Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish.

PubMed

Egan, Rupert J; Bergner, Carisa L; Hart, Peter C; Cachat, Jonathan M; Canavello, Peter R; Elegante, Marco F; Elkhayat, Salem I; Bartels, Brett K; Tien, Anna K; Tien, David H; Mohnot, Sopan; Beeson, Esther; Glasgow, Eric; Amri, Hakima; Zukowska, Zofia; Kalueff, Allan V

2009-12-14

The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and high-throughput model of stress and affective disorders.

Roles of inter-individual differences and intra-individual acute elevations in early smoking lapse in people with posttraumatic stress disorder.

PubMed

Dedert, Eric A; Hicks, Terrell A; Dennis, Paul A; Calhoun, Patrick S; Beckham, Jean C

2016-09-01

Existing models of the role of posttraumatic stress disorder (PTSD) symptoms and smoking have almost exclusively examined mean symptom levels, rather than the acute elevations that might trigger smoking lapse immediately or increase risk of a smoking lapse in the next few hours. We examined ecological momentary assessments (EMA) of PTSD symptom clusters and smoking in the first week of a quit attempt in 52 people with PTSD. In multilevel models including PTSD symptom means, acute elevations, and lagged acute elevations together as simultaneous predictors of odds of smoking in the same models, pre-quit smoking occasions were significantly related to acute elevations in symptoms, including PTSD totals (OR=1.20; 95% CI, 1.10 to 1.31), PTSD re-experiencing symptoms (OR=1.16; 95% CI, 1.06 to 1.27), PTSD avoidance symptoms (OR=1.20; 95% CI, 1.10 to 1.31), PTSD numbing symptoms (OR=1.14; 95% CI, 1.04 to 1.24), and PTSD hyperarousal symptoms (OR=1.20; 95% CI, 1.09 to 1.31). In contrast, post-quit smoking was related to lagged acute elevations in PTSD re-experiencing (OR=1.24, 95% CI, 1.03 to 1.50) avoidance (OR=1.27, 95% CI, 1.05 to 1.53), and numbing symptoms (OR=1.24, 95% CI, 1.02 to 1.51). During a quit attempt, individuals with PTSD delayed smoking in response to acute elevations in PTSD re-experiencing and Avoidance. This period presents an opportunity to use mobile health interventions to prevent smoking lapse and to use coping skills acquired in trauma-focused therapy to respond to acute PTSD symptom elevation. Published by Elsevier Ltd.

Experiences of Physical Therapists Working in the Acute Hospital Setting: Systematic Review.

PubMed

Lau, Bonnie; Skinner, Elizabeth H; Lo, Kristin; Bearman, Margaret

2016-09-01

Physical therapists working in acute care hospitals require unique skills to adapt to the challenging environment and short patient length of stay. Previous literature has reported burnout of clinicians and difficulty with staff retention; however, no systematic reviews have investigated qualitative literature in the area. The purpose of this study was to investigate the experiences of physical therapists working in acute hospitals. Six databases (MEDLINE, CINAHL Plus, EMBASE, AMED, PsycINFO, and Sociological Abstracts) were searched up to and including September 30, 2015, using relevant terms. Studies in English were selected if they included physical therapists working in an acute hospital setting, used qualitative methods, and contained themes or descriptive data relating to physical therapists' experiences. Data extraction included the study authors and year, settings, participant characteristics, aims, and methods. Key themes, explanatory models/theories, and implications for policy and practice were extracted, and quality assessment was conducted. Thematic analysis was used to conduct qualitative synthesis. Eight articles were included. Overall, study quality was high. Four main themes were identified describing factors that influence physical therapists' experience and clinical decision making: environmental/contextual factors, communication/relationships, the physical therapist as a person, and professional identity/role. Qualitative synthesis may be difficult to replicate. The majority of articles were from North America and Australia, limiting transferability of the findings. The identified factors, which interact to influence the experiences of acute care physical therapists, should be considered by therapists and their managers to optimize the physical therapy role in acute care. Potential strategies include promotion of interprofessional and collegial relationships, clear delineation of the physical therapy role, multidisciplinary team member education, additional support staff, and innovative models of care to address funding and staff shortages. © 2016 American Physical Therapy Association.

Prospects of apoptotic cell-based therapies for transplantation and inflammatory diseases.

PubMed

Saas, Philippe; Kaminski, Sandra; Perruche, Sylvain

2013-10-01

Apoptotic cell removal or interactions of early-stage apoptotic cells with immune cells are associated with an immunomodulatory microenvironment that can be harnessed to exert therapeutic effects. While the involved immune mechanisms are still being deciphered, apoptotic cell infusion has been tested in different experimental models where inflammation is deregulated. This includes chronic and acute inflammatory disorders such as arthritis, contact hypersensitivity and acute myocardial infarction. Apoptotic cell infusion has also been used in transplantation settings to prevent or treat acute and chronic rejection, as well as to limit acute graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Here, we review the mechanisms involved in apoptotic cell-induced immunomodulation and data obtained in preclinical models of transplantation and inflammatory diseases.

Impact Analysis of Age on Fallout Fatality Estimations for IND Scenarios

DTIC Science & Technology

2017-11-30

management of the acute radiation syndrome : recommendations of the Strategic National Stockpile Radiation Working Group. Ann Intern Med 140: 1037-51...dependent radiation dose response for acute effects was evaluated in detail. The analysis included data from animal studies, radiation oncology, and other...probability of 60-day mortality (assuming no treatment) for acute radiation exposure. This model has been adapted to account for protracted fallout

The Future Impact of Vietnam Era Veterans on Inpatient Acute Care and Mental Health Product Lines at a Veterans Affairs Medical Center

DTIC Science & Technology

2000-06-20

smoothing and regression which includes curve fitting are two principle forecasting model types utilized in the vast majority of forecasting applications ... model were compared against the VA Office of Policy and Planning forecasting study commissioned with the actuarial firm of Milliman & Robertson (M & R... Application to the Veterans Healthcare System The development of a model to forecast future VEV needs, utilization, and cost of the Acute Care and

Underbody Blast Models of TBI Caused by Hyper-Acceleration and Secondary Head Impact

DTIC Science & Technology

2014-02-01

Cleveland RO, Tanzi RE, Stanton PK, McKee AC. (2012) Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model...exposure, remove brains, and process for electron microscopic analysis of cyto- and axonal ultrastructure and for histochemical evidence of acute ...of Trauma and Acute Care Surgery (see Appendix). These observations include increased axonopathy (silver staining) in the cerebellum and astrocyte

Development of a Multicomponent Prediction Model for Acute Esophagitis in Lung Cancer Patients Receiving Chemoradiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Ruyck, Kim, E-mail: kim.deruyck@UGent.be; Sabbe, Nick; Oberije, Cary

2011-10-01

Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical center. Treatment parameters included chemotherapy, surgery, radiotherapy technique, tumor dose, mean fractionation size, mean and maximal esophageal dose, and overall treatment time. A total of 332 genetic polymorphisms were considered in 112 candidatemore » genes. The predicting model was achieved by lasso logistic regression for predictor selection, followed by classic logistic regression for unbiased estimation of the coefficients. Performance of the model was expressed as the area under the curve of the receiver operating characteristic and as the false-negative rate in the optimal point on the receiver operating characteristic curve. Results: A total of 110 patients (40%) developed acute esophagitis Grade {>=}2 (Common Terminology Criteria for Adverse Events v3.0). The final model contained chemotherapy treatment, lymph node stage, mean esophageal dose, gender, overall treatment time, radiotherapy technique, rs2302535 (EGFR), rs16930129 (ENG), rs1131877 (TRAF3), and rs2230528 (ITGB2). The area under the curve was 0.87, and the false-negative rate was 16%. Conclusion: Prediction of acute esophagitis can be improved by combining clinical, treatment, and genetic factors. A multicomponent prediction model for acute esophagitis with a sensitivity of 84% was constructed with two clinical parameters, four treatment parameters, and four genetic polymorphisms.« less

Aging models of acute seizures and epilepsy.

PubMed

Kelly, Kevin M

2010-01-01

Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute seizures and epilepsy in the elderly. To date, there have been relatively few studies dedicated to the modeling of acute seizures and epilepsy in aged, healthy animals. Inherent challenges to this area of research include the costs associated with the purchase and maintenance of older animals and, at times, the unexpected and potentially confounding comorbidities associated with aging. However, recent studies using a variety of in vivo and in vitro models of acute seizures and epilepsy in mice and rats have built upon early investigations in the field, all of which has provided an expanded vision of seizure generation and epileptogenesis in the aged brain. Results of these studies could potentially translate to new and tailored interventional approaches that limit or prevent the development of epilepsy in the elderly.

External Validation of a Case-Mix Adjustment Model for the Standardized Reporting of 30-Day Stroke Mortality Rates in China.

PubMed

Yu, Ping; Pan, Yuesong; Wang, Yongjun; Wang, Xianwei; Liu, Liping; Ji, Ruijun; Meng, Xia; Jing, Jing; Tong, Xu; Guo, Li; Wang, Yilong

2016-01-01

A case-mix adjustment model has been developed and externally validated, demonstrating promise. However, the model has not been thoroughly tested among populations in China. In our study, we evaluated the performance of the model in Chinese patients with acute stroke. The case-mix adjustment model A includes items on age, presence of atrial fibrillation on admission, National Institutes of Health Stroke Severity Scale (NIHSS) score on admission, and stroke type. Model B is similar to Model A but includes only the consciousness component of the NIHSS score. Both model A and B were evaluated to predict 30-day mortality rates in 13,948 patients with acute stroke from the China National Stroke Registry. The discrimination of the models was quantified by c-statistic. Calibration was assessed using Pearson's correlation coefficient. The c-statistic of model A in our external validation cohort was 0.80 (95% confidence interval, 0.79-0.82), and the c-statistic of model B was 0.82 (95% confidence interval, 0.81-0.84). Excellent calibration was reported in the two models with Pearson's correlation coefficient (0.892 for model A, p<0.001; 0.927 for model B, p = 0.008). The case-mix adjustment model could be used to effectively predict 30-day mortality rates in Chinese patients with acute stroke.

St George Acute Care Team: the local variant of crisis resolution model of care.

PubMed

Cupina, Denise D; Wand, Anne P F; Phelan, Emma; Atkin, Rona

2016-10-01

The objective of this study was to describe functioning and clinical activities of the St George Acute Care Team and how it compares to the typical crisis resolution model of care. Descriptive data including demographics, sources of referral, type of clinical intervention, length of stay, diagnoses and outcomes were collected from records of all patients who were discharged from the team during a 10 week period. There were 677 referrals. The team's functions consisted of post-discharge follow-up (31%), triage and intake (30%), case management support (23%) and acute community based assessment and treatment (16%). The average length of stay was 5 days. The majority of patients were diagnosed with a mood (23%) or a psychotic (25%) disorder. Points of contrast to other reported crisis resolution teams include shorter length of stay, relatively less focus on direct clinical assessment and more telephone follow-up and triage. St George Acute Care Team provides a variety of clinical activities. The focus has shifted away from the original model of crisis resolution care to meet local and governmental requirements. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury

PubMed Central

Pannu, Neesh; Hemmelgarn, Brenda R.; Austin, Peter C.; Tan, Zhi; McArthur, Eric; Manns, Braden J.; Tonelli, Marcello; Wald, Ron; Quinn, Robert R.; Ravani, Pietro; Garg, Amit X.

2017-01-01

Importance Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. Objective To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Design, Setting, and Participants Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Exposures Demographic, laboratory, and comorbidity variables measured prior to discharge. Main Outcomes and Measures Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. Results The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%). Conclusions and Relevance A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research. PMID:29136443

Derivation and External Validation of Prediction Models for Advanced Chronic Kidney Disease Following Acute Kidney Injury.

PubMed

James, Matthew T; Pannu, Neesh; Hemmelgarn, Brenda R; Austin, Peter C; Tan, Zhi; McArthur, Eric; Manns, Braden J; Tonelli, Marcello; Wald, Ron; Quinn, Robert R; Ravani, Pietro; Garg, Amit X

2017-11-14

Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up. To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease. Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013). Demographic, laboratory, and comorbidity variables measured prior to discharge. Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year. The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%). A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research.

AP214, an analogue of α-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

PubMed Central

Doi, Kent; Hu, Xuzhen; Yuen, Peter S.T.; Leelahavanichkul, Asada; Yasuda, Hideo; Kim, Soo Mi; Schnermann, Jürgen; Jonassen, Thomas E.N.; Frøkiær, Jørgen; Nielsen, Søren; Star, Robert A.

2008-01-01

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. α-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new α-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 hr after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-α and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-κB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. PMID:18354376

Inflammation in acute and chronic pancreatitis.

PubMed

Habtezion, Aida

2015-09-01

This report reviews recent animal model and human studies associated with inflammatory responses in acute and chronic pancreatitis. Animal model and limited human acute and chronic pancreatitis studies unravel the dynamic nature of the inflammatory processes and the ability of the immune cells to sense danger and environmental signals. In acute pancreatitis, such molecules include pathogen-associated molecular pattern recognition receptors such as toll-like receptors, and the more recently appreciated damage-associated molecular pattern molecules or 'alarmin' high mobility group box 1 and IL-33. In chronic pancreatitis, a recent understanding of a critical role for macrophage-pancreatic stellate cell interaction offers a potential targetable pathway that can alter fibrogenesis. Microbiome research in pancreatitis is a new field gaining interest but will require further investigation. Immune cell contribution to the pathogenesis of acute and chronic pancreatitis is gaining more appreciation and further understanding in immune signaling presents potential therapeutic targets that can alter disease progression.

PREDICTION OF POPULATION-LEVEL RESPONSE FROM MYSID TOXICITY TEST DATA USING POPULATION MODEL TECHNIQUES

EPA Science Inventory

Acute and chronic bioassay statistics are used to evaluate the toxicity and the risks of chemical stressors to mysid shrimp Americamysis bahia (formerly Mysidopsis bahia). These include LC50 values from acute tests, chronic values (the geometric mean of the no-obsderved-effect co...

Severe oxidative stress in an acute inflammatory demyelinating model in the rhesus monkey.

PubMed

Dunham, Jordon; van de Vis, Reinofke; Bauer, Jan; Wubben, Jacqueline; van Driel, Nikki; Laman, Jon D; 't Hart, Bert A; Kap, Yolanda S

2017-01-01

Oxidative stress is increasingly implicated as a co-factor of tissue injury in inflammatory/demyelinating disorders of the central nervous system (CNS), such as multiple sclerosis (MS). While rodent experimental autoimmune encephalomyelitis (EAE) models diverge from human demyelinating disorders with respect to limited oxidative injury, we observed that in a non-human primate (NHP) model for MS, namely EAE in the common marmoset, key pathological features of the disease were recapitulated, including oxidative tissue injury. Here, we investigated the presence of oxidative injury in another NHP EAE model, i.e. in rhesus macaques, which yields an acute demyelinating disease, which may more closely resemble acute disseminated encephalomyelitis (ADEM) than MS. Rhesus monkey EAE diverges from marmoset EAE by abundant neutrophil recruitment into the CNS and destructive injury to white matter. This difference prompted us to investigate to which extent the oxidative pathway features elicited in MS and marmoset EAE are reflected in the acute rhesus monkey EAE model. The rhesus EAE brain was characterized by widespread demyelination and active lesions containing numerous phagocytic cells and to a lesser extent T cells. We observed induction of the oxidative stress pathway, including injury, with a predilection of p22phox expression in neutrophils and macrophages/microglia. In addition, changes in iron were observed. These results indicate that pathogenic mechanisms in the rhesus EAE model may differ from the marmoset EAE and MS brain due to the neutrophil involvement, but may in the end lead to similar induction of oxidative stress and injury.

Immune-modulating therapy in acute pancreatitis: Fact or fiction

PubMed Central

Akinosoglou, Karolina; Gogos, Charalambos

2014-01-01

Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future. PMID:25386069

The impact and effectiveness of nurse-led care in the management of acute and chronic pain: a review of the literature.

PubMed

Courtenay, Molly; Carey, Nicola

2008-08-01

To identify, summarise and critically appraise the current evidence regarding the impact and effectiveness of nurse-led care in acute and chronic pain. A diverse range of models of care exist within the services available for the management of acute and chronic pain. Primary studies have been conducted evaluating these models, but, review and synthesis of the findings from these studies has not been undertaken. Literature review. Searches of Pubmed (NLM) Medline, CINAHL, Web of Knowledge (Science Index, Social Science index), British Nursing Index from January 1996-March 2007 were conducted. The searches were supplemented by an extensive hand search of the literature through references identified from retrieved articles and by contact with experts in the field. Twenty-one relevant publications were identified and included findings from both primary and secondary care. The areas, in which nurses, caring for patients in pain are involved, include assessment, monitoring, evaluation of pain, interdisciplinary collaboration and medicines management. Education programmes delivered by specialist nurses can improve the assessment and documentation of acute and chronic pain. Educational interventions and the use of protocols by specialist nurses can improve patients understanding of their condition and improve pain control. Acute pain teams, led by nurses, can reduce pain intensity and are cost effective. Nurses play key roles in the diverse range of models of care that exist in acute and chronic pain. However, there are methodological weaknesses across this body of research evidence and under researched issues that point to a need for further rigorous evaluation. Nurse-led care is an integral element of the pain services offered to patients. This review highlights the effect of this care and the issues that require consideration by those responsible for the development of nurse-led models in acute and chronic pain.

Current Risk Adjustment and Comorbidity Index Underperformance in Predicting Post-Acute Utilization and Hospital Readmissions After Joint Replacements: Implications for Comprehensive Care for Joint Replacement Model.

PubMed

Kumar, Amit; Karmarkar, Amol; Downer, Brian; Vashist, Amit; Adhikari, Deepak; Al Snih, Soham; Ottenbacher, Kenneth

2017-11-01

To compare the performances of 3 comorbidity indices, the Charlson Comorbidity Index, the Elixhauser Comorbidity Index, and the Centers for Medicare & Medicaid Services (CMS) risk adjustment model, Hierarchical Condition Category (HCC), in predicting post-acute discharge settings and hospital readmission for patients after joint replacement. A retrospective study of Medicare beneficiaries with total knee replacement (TKR) or total hip replacement (THR) discharged from hospitals in 2009-2011 (n = 607,349) was performed. Study outcomes were post-acute discharge setting and unplanned 30-, 60-, and 90-day hospital readmissions. Logistic regression models were built to compare the performance of the 3 comorbidity indices using C statistics. The base model included patient demographics and hospital use. Subsequent models included 1 of the 3 comorbidity indices. Additional multivariable logistic regression models were built to identify individual comorbid conditions associated with high risk of hospital readmissions. The 30-, 60-, and 90-day unplanned hospital readmission rates were 5.3%, 7.2%, and 8.5%, respectively. Patients were most frequently discharged to home health (46.3%), followed by skilled nursing facility (40.9%) and inpatient rehabilitation facility (12.7%). The C statistics for the base model in predicting post-acute discharge setting and 30-, 60-, and 90-day readmission in TKR and THR were between 0.63 and 0.67. Adding the Charlson Comorbidity Index, the Elixhauser Comorbidity Index, or HCC increased the C statistic minimally from the base model for predicting both discharge settings and hospital readmission. The health conditions most frequently associated with hospital readmission were diabetes mellitus, pulmonary disease, arrhythmias, and heart disease. The comorbidity indices and CMS-HCC demonstrated weak discriminatory ability to predict post-acute discharge settings and hospital readmission following joint replacement. © 2017, American College of Rheumatology.

Evaluation of cerebral-cardiac syndrome using echocardiography in a canine model of acute traumatic brain injury.

PubMed

Qian, Rong; Yang, Weizhong; Wang, Xiumei; Xu, Zhen; Liu, Xiaodong; Sun, Bing

2015-01-01

Previous studies have confirmed that traumatic brain injury (TBI) can induce general adaptation syndrome (GAS), which subsequently results in myocardial dysfunction and damage in some patients with acute TBI; this condition is also termed as cerebral-cardiac syndrome. However, most clinicians ignore the detection and treatment of myocardial dysfunction, and instead concentrate only on the serious neural damage that is observed in acute TBI, which is one of the most important fatal factors. Therefore, clarification is urgently needed regarding the relationship between TBI and myocardial dysfunction. In the present study, we evaluated 18 canine models of acute TBI, by using real-time myocardial contrast echocardiography and strain rate imaging to accurately evaluate myocardial function and regional microcirculation, including the strain rate of the different myocardial segments, time-amplitude curves, mean ascending slope of the curve, and local myocardial blood flow. Our results suggest that acute TBI often results in cerebral-cardiac syndrome, which rapidly progresses to the serious stage within 3 days. This study is the first to provide comprehensive ultrasonic characteristics of cerebral-cardiac syndrome in an animal model of TBI.

External Validation of a Case-Mix Adjustment Model for the Standardized Reporting of 30-Day Stroke Mortality Rates in China

PubMed Central

Yu, Ping; Pan, Yuesong; Wang, Yongjun; Wang, Xianwei; Liu, Liping; Ji, Ruijun; Meng, Xia; Jing, Jing; Tong, Xu; Guo, Li; Wang, Yilong

2016-01-01

Background and Purpose A case-mix adjustment model has been developed and externally validated, demonstrating promise. However, the model has not been thoroughly tested among populations in China. In our study, we evaluated the performance of the model in Chinese patients with acute stroke. Methods The case-mix adjustment model A includes items on age, presence of atrial fibrillation on admission, National Institutes of Health Stroke Severity Scale (NIHSS) score on admission, and stroke type. Model B is similar to Model A but includes only the consciousness component of the NIHSS score. Both model A and B were evaluated to predict 30-day mortality rates in 13,948 patients with acute stroke from the China National Stroke Registry. The discrimination of the models was quantified by c-statistic. Calibration was assessed using Pearson’s correlation coefficient. Results The c-statistic of model A in our external validation cohort was 0.80 (95% confidence interval, 0.79–0.82), and the c-statistic of model B was 0.82 (95% confidence interval, 0.81–0.84). Excellent calibration was reported in the two models with Pearson’s correlation coefficient (0.892 for model A, p<0.001; 0.927 for model B, p = 0.008). Conclusions The case-mix adjustment model could be used to effectively predict 30-day mortality rates in Chinese patients with acute stroke. PMID:27846282

Post-acute referral patterns for hospitals and implications for bundled payment initiatives.

PubMed

Lau, Christopher; Alpert, Abby; Huckfeldt, Peter; Hussey, Peter; Auerbach, David; Liu, Hangsheng; Sood, Neeraj; Mehrotra, Ateev

2014-09-01

Under new bundled payment models, hospitals are financially responsible for post-acute care delivered by providers such as skilled nursing facilities (SNFs) and home health agencies (HHAs). The hope is that hospitals will use post-acute care more prudently and better coordinate care with post-acute providers. However, little is known about existing patterns in hospitals׳ referrals to post-acute providers. Post-acute provider referrals were identified using SNF and HHA claims within 14 days following hospital discharge. Hospital post-acute care network size and concentration were estimated across hospital types and regions. The 2008 Medicare Provider Analysis and Review claims for acute hospitals and SNFs, and the 100% HHA Standard Analytic Files were used. The mean post-acute care network size for U.S. hospitals included 57.9 providers with 37.5 SNFs and 23.4 HHAs. The majority of these providers (65.7% of SNFs, 60.9% of HHAs) accounted for 1 percent or less of a hospital׳s referrals and classified as "low-volume". Other post-acute providers we classified as routine. The mean network size for routine providers was greater for larger hospitals, teaching hospitals and in regions with higher per capita post-acute care spending. The average hospital works with over 50 different post-acute providers. Moreover, the size of post-acute care networks varies considerably geographically and by hospital characteristics. These results provide context on the complex task hospitals will face in coordinating care with post-acute providers and cutting costs under new bundled payment models. Copyright © 2014 Elsevier Inc. All rights reserved.

Predictors of mental health-related acute service utilisation and treatment costs in the 12 months following an acute psychiatric admission.

PubMed

Siskind, Dan; Harris, Meredith; Diminic, Sandra; Carstensen, Georgia; Robinson, Gail; Whiteford, Harvey

2014-11-01

A key step in informing mental health resource allocation is to identify the predictors of service utilisation and costs. This project aims to identify the predictors of mental health-related acute service utilisation and treatment costs in the year following an acute public psychiatric hospital admission. A dataset containing administrative and routinely measured outcome data for 1 year before and after an acute psychiatric admission for 1757 public mental health patients was analysed. Multivariate regression models were developed to identify patient- and treatment-related predictors of four measures of service utilisation or cost: (a) duration of index admission; and, in the year after discharge from the index admission (b) acute psychiatric inpatient bed-days; (c) emergency department (ED) presentations; and (d) total acute mental health service costs. Split-sample cross-validation was used. A diagnosis of psychosis, problems with living conditions and prior acute psychiatric inpatient bed-days predicted a longer duration of index admission, while prior ED presentations and self-harm predicted a shorter duration. A greater number of acute psychiatric inpatient bed-days in the year post-discharge were predicted by psychosis diagnosis, problems with living conditions and prior acute psychiatric inpatient admissions. The number of future ED presentations was predicted by past ED presentations. For total acute care costs, diagnosis of psychosis was the strongest predictor. Illness acuity and prior acute psychiatric inpatient admission also predicted higher costs, while self-harm predicted lower costs. The development of effective models for predicting acute mental health treatment costs using existing administrative data is an essential step towards a workable activity-based funding model for mental health. Future studies would benefit from the inclusion of a wider range of variables, including ethnicity, clinical complexity, cognition, mental health legal status, electroconvulsive therapy, problems with activities of daily living and community contacts. © The Royal Australian and New Zealand College of Psychiatrists 2014.

The acute gastrointestinal subsyndrome of the acute radiation syndrome: a rhesus macaque model.

PubMed

MacVittie, Thomas J; Farese, Ann M; Bennett, Alexander; Gelfond, Daniel; Shea-Donohue, Terez; Tudor, Gregory; Booth, Catherine; McFarland, Emylee; Jackson, William

2012-10-01

The development of medical countermeasures against the acute gastrointestinal subsyndrome of the acute radiation syndrome in humans requires well characterized and validated animal models. These models must adhere to the criteria of the U.S. Food and Drug Administration's Animal Rule and consider the natural history and clinical context of the human radiation response and treatment in the nuclear terrorist scenario. The models must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity, including concurrent damage in other organs, such as the bone marrow, that may contribute to the overall mortality and morbidity. There are no such models of the gastrointestinal syndrome in response to total-body irradiation in the nonhuman primate. Herein, these parameters are defined for the rhesus macaque exposed to potentially lethal doses of radiation and administered medical management. Rhesus macaques (n = 69) were exposed bilaterally to 6 MV linear accelerator-derived photon total body irradiation to midline tissue (thorax) doses ranging from 10.0 to 14.0 Gy at 0.80 Gy min(-1). Following irradiation, all animals were administered supportive care consisting of fluids, anti-emetics, anti-diarrheal medication, antibiotics, blood transfusions, analgesics, and nutrition. The primary endpoint was survival at 15 d post-irradiation. Secondary endpoints included indices of dehydration, diarrhea, weight loss, hematological parameters, cellular histology of the small and large intestine, and mean survival time of decedents. Mortality within the 15-d in vivo study defined the acute gastrointestinal syndrome and provided an LD30/15 of 10.76 Gy, LD50/15 of 11.33 Gy, and an LD70/15 of 11.90 Gy. Intestinal crypt and villus loss were dose- and time-dependent with an apparent nadir 7 d post-irradiation and recovery noted thereafter. Severe myelosuppression and thrombocytopenia were noted in all animals, requiring the administration of antibiotics and blood transfusions. The model defines the dose response relationship and time course of acute gastrointestinal syndrome-induced morbidity and mortality in the rhesus macaque.

[Application of a continual improvement approach to selecting diagnostic markers for acute pancreatitis in an emergency department].

PubMed

Salinas, María; Flores, Emilio; López-Garrigós, Maite; Díaz, Elena; Esteban, Patricia; Leiva-Salinas, Carlos

2017-01-01

To apply a continual improvement model to develop an algorithm for ordering laboratory tests to diagnose acute pancreatitis in a hospital emergency department. Quasi-experimental study using the continual improvement model (plan, do, check, adjust cycles) in 2 consecutive phases in emergency patients: amylase and lipase results were used to diagnose acute pancreatitis in the first phase; in the second, only lipase level was first determined; amylase testing was then ordered only if the lipase level fell within a certain range. We collected demographic data, number amylase and lipase tests ordered and the findings, final diagnosis, and the results of a questionnaire to evaluate satisfaction with emergency care. The first phase included 517 patients, of whom 20 had acute pancreatitis. For amylase testing sensitivity was 0.70; specificity, 0.85; positive predictive value (PPV), 17; and negative predictive value (NPV), 0.31. For lipase testing these values were sensitivity, 0.85; specificity, 0.96; PPV, 21, and NPV, 0.16. When both tests were done, sensitivity was 0.85; specificity 0.99; PPV, 85; and NPV, 0.15. The second phase included data for 4815 patients, 118 of whom had acute pancreatitis. The measures of diagnostic yield for the new algorithm were sensitivity, 0.92; specificity, 0.98; PPV, 46; and NPV, 0.08]. This study demonstrates a process for developing a protocol to guide laboratory testing in acute pancreatitis in the hospital emergency department. The proposed sequence of testing for pancreatic enzyme levels can be effective for diagnosing acute pancreatitis in patients with abdominal pain.

Hospital Variation in Intensive Care Resource Utilization and Mortality in Newly Diagnosed Pediatric Leukemia.

PubMed

Fitzgerald, Julie C; Li, Yimei; Fisher, Brian T; Huang, Yuan-Shung; Miller, Tamara P; Bagatell, Rochelle; Seif, Alix E; Aplenc, Richard; Thomas, Neal J

2018-06-01

To evaluate hospital-level variability in resource utilization and mortality in children with new leukemia who require ICU support, and identify factors associated with variation. Retrospective cohort study. Children's hospitals contributing to the Pediatric Health Information Systems administrative database from 1999 to 2011. Inpatients less than 25 years old with newly diagnosed acute lymphocytic leukemia or acute myeloid leukemia requiring ICU support (n = 1,754). Evaluated exposures included leukemia type, year of diagnosis, and hospital-wide proportion of patients with public insurance. The main outcome was hospital mortality. Wide variability existed in the ICU resources used across hospitals. Combined acute lymphocytic leukemia and acute myeloid leukemia mortality varied by hospital from 0% (95% CI, 0-14.8%) to 42.9% (95% CI, 17.7-71.1%). A mixed-effects model with a hospital-level random effect suggests significant variation across hospitals in mortality (p = 0.007). When including patient and hospital factors as fixed effects into the model, younger age, acute myeloid leukemia versus acute lymphocytic leukemia diagnosis, leukemia diagnosis prior to 2005, hospital-wide proportion of public insurance patients, and hospital-level proportion of leukemia patients receiving ICU care are significantly associated with mortality. The variation across hospitals remains significant with all patient factors included (p = 0.021) but is no longer significant after adjusting for the hospital-level factors proportion of public insurance and proportion receiving ICU care (p = 0.48). Wide hospital-level variability in ICU resource utilization and mortality exists in the care of children with leukemia requiring ICU support. Hospital payer mix is associated with some mortality variability. Additional study into how ICU support could be standardized through clinical practice guidelines, impact of payer mix on hospital resources allocation to the ICU, and subsequent impact on patient outcomes is warranted.

Use of Animal Models to Develop Antiaddiction Medications

PubMed Central

Gardner, Eliot L.

2008-01-01

Although addiction is a uniquely human phenomenon, some of its pathognomonic features can be modeled at the animal level. Such features include the euphoric “high” produced by acute administration of addictive drugs; the dysphoric “crash” produced by acute withdrawal, drug-seeking, and drug-taking behaviors; and relapse to drug-seeking behavior after achieving successful abstinence. Animal models exist for each of these features. In this review, I focus on various animal models of addiction and how they can be used to search for clinically effective antiaddiction medications. I conclude by noting some of the new and novel medications that have been developed preclinically using such models and the hope for further developments along such lines. PMID:18803910

Multi-center prediction of hemorrhagic transformation in acute ischemic stroke using permeability imaging features.

PubMed

Scalzo, Fabien; Alger, Jeffry R; Hu, Xiao; Saver, Jeffrey L; Dani, Krishna A; Muir, Keith W; Demchuk, Andrew M; Coutts, Shelagh B; Luby, Marie; Warach, Steven; Liebeskind, David S

2013-07-01

Permeability images derived from magnetic resonance (MR) perfusion images are sensitive to blood-brain barrier derangement of the brain tissue and have been shown to correlate with subsequent development of hemorrhagic transformation (HT) in acute ischemic stroke. This paper presents a multi-center retrospective study that evaluates the predictive power in terms of HT of six permeability MRI measures including contrast slope (CS), final contrast (FC), maximum peak bolus concentration (MPB), peak bolus area (PB), relative recirculation (rR), and percentage recovery (%R). Dynamic T2*-weighted perfusion MR images were collected from 263 acute ischemic stroke patients from four medical centers. An essential aspect of this study is to exploit a classifier-based framework to automatically identify predictive patterns in the overall intensity distribution of the permeability maps. The model is based on normalized intensity histograms that are used as input features to the predictive model. Linear and nonlinear predictive models are evaluated using a cross-validation to measure generalization power on new patients and a comparative analysis is provided for the different types of parameters. Results demonstrate that perfusion imaging in acute ischemic stroke can predict HT with an average accuracy of more than 85% using a predictive model based on a nonlinear regression model. Results also indicate that the permeability feature based on the percentage of recovery performs significantly better than the other features. This novel model may be used to refine treatment decisions in acute stroke. Copyright © 2013 Elsevier Inc. All rights reserved.

Zebrafish is a predictive model for identifying compounds that protect against brain toxicity in severe acute organophosphorus intoxication.

PubMed

Faria, Melissa; Prats, Eva; Padrós, Francesc; Soares, Amadeu M V M; Raldúa, Demetrio

2017-04-01

Acute organophosphorus (OP) intoxication is a worldwide clinical and public health problem. In addition to cholinergic crisis, neurodegeneration and brain damage are hallmarks of the severe form of this toxidrome. Recently, we generated a chemical model of severe acute OP intoxication in zebrafish that is characterized by altered head morphology and brain degeneration. The pathophysiological pathways resulting in brain toxicity in this model are similar to those described in humans. The aim of this study was to assess the predictive power of this zebrafish model by testing the effect of a panel of drugs that provide protection in mammalian models. The selected drugs included "standard therapy" drugs (atropine and pralidoxime), reversible acetylcholinesterase inhibitors (huperzine A, galantamine, physostigmine and pyridostigmine), N-methyl-D-aspartate (NMDA) receptor antagonists (MK-801 and memantine), dual-function NMDA receptor and acetylcholine receptor antagonists (caramiphen and benactyzine) and anti-inflammatory drugs (dexamethasone and ibuprofen). The effects of these drugs on zebrafish survival and the prevalence of abnormal head morphology in the larvae exposed to 4 µM chlorpyrifos oxon [1 × median lethal concentration (LC 50 )] were determined. Moreover, the neuroprotective effects of pralidoxime, memantine, caramiphen and dexamethasone at the gross morphological level were confirmed by histopathological and transcriptional analyses. Our results demonstrated that the zebrafish model for severe acute OP intoxication has a high predictive value and can be used to identify new compounds that provide neuroprotection against severe acute OP intoxication.

The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

PubMed

MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

2012-10-01

The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for efficacy and interaction during the concomitant evolution of acute and delayed key organ-specific subsyndromes.

MRI-Based Neuroanatomical Predictors of Dysphagia, Dysarthria, and Aphasia in Patients with First Acute Ischemic Stroke
.

PubMed

Flowers, Heather L; AlHarbi, Mohammed A; Mikulis, David; Silver, Frank L; Rochon, Elizabeth; Streiner, David; Martino, Rosemary

2017-01-01

Due to the high post-stroke frequency of dysphagia, dysarthria, and aphasia, we developed comprehensive neuroanatomical, clinical, and demographic models to predict their presence after acute ischemic stroke. The sample included 160 randomly selected first-ever stroke patients with confirmed infarction on magnetic resonance imaging from 1 tertiary stroke center. We documented acute lesions within 12 neuroanatomical regions and their associated volumes. Further, we identified concomitant chronic brain disease, including atrophy, white matter hyperintensities, and covert strokes. We developed predictive models using logistic regression with odds ratios (OR) and their 95% confidence intervals (95% CI) including demographic, clinical, and acute and chronic neuroanatomical factors. Predictors of dysphagia included medullary (OR 6.2, 95% CI 1.5-25.8), insular (OR 4.8, 95% CI 2.0-11.8), and pontine (OR 3.6, 95% CI 1.2-10.1) lesions, followed by brain atrophy (OR 3.0, 95% CI 1.04-8.6), internal capsular lesions (OR 2.9, 95% CI 1.2-6.6), and increasing age (OR 1.4, 95% CI 1.1-1.8). Predictors of dysarthria included pontine (OR 7.8, 95% CI 2.7-22.9), insular (OR 4.5, 95% CI 1.8-11.4), and internal capsular (OR 3.6, 95% CI 1.6-7.9) lesions. Predictors of aphasia included left hemisphere insular (OR 34.4, 95% CI 4.2-283.4), thalamic (OR 6.2, 95% CI 1.6-24.4), and cortical middle cerebral artery (OR 4.7, 95% CI 1.5-14.2) lesions. Predicting outcomes following acute stroke is important for treatment decisions. Determining the risk of major post-stroke impairments requires consideration of factors beyond lesion localization. Accordingly, we demonstrated interactions between localized and global brain function for dysphagia and elucidated common lesion locations across 3 debilitating impairments.
. © 2017 The Author(s)
. Published by S. Karger AG, Basel.

Advanced practice nursing role delineation in acute and critical care: application of the strong model of advanced practice.

PubMed

Mick, D J; Ackerman, M H

2000-01-01

This purpose of this study was to differentiate between the roles of clinical nurse specialists and acute care nurse practitioners. Hypothesized blending of the clinical nurse specialist and acute care nurse practitioner roles is thought to result in an acute care clinician who integrates the clinical skills of the nurse practitioner with the systems knowledge, educational commitment, and leadership ability of the clinical nurse specialist. Ideally, this role blending would facilitate excellence in both direct and indirect patient care. The Strong Model of Advanced Practice, which incorporates practice domains of direct comprehensive care, support of systems, education, research, and publication and professional leadership, was tested to search for practical evidence of role blending. This descriptive, exploratory, pilot study included subjects (N = 18) solicited from an academic medical center and from an Internet advanced practice listserv. Questionnaires included self-ranking of expertise in practice domains, as well as valuing of role-related tasks. Content validity was judged by an expert panel of advanced practice nurses. Analyses of descriptive statistics revealed that clinical nurse specialists, who had more experience both as registered nurses and in the advanced practice nurse role, self-ranked their expertise higher in all practice domains. Acute care nurse practitioners placed higher importance on tasks related to direct comprehensive care, including conducting histories and physicals, diagnosing, and performing diagnostic procedures, whereas clinical nurse specialists assigned greater importance to tasks related to education, research, and leadership. Levels of self-assessed clinical expertise as well as valuing of role-related tasks differed among this sample of clinical nurse specialists and acute care nurse practitioners. Groundwork has been laid for continuing exploration into differentiation in advanced practice nursing roles. As the clinical nurse specialist role changes and the acute care nurse practitioner role emerges, it is imperative that advanced practice nurses describe their contribution to health care. Associating advanced practice nursing activities with outcomes will help further characterize these 2 advanced practice roles.

Costs of terminal patients who receive palliative care or usual care in different hospital wards.

PubMed

Simoens, Steven; Kutten, Betty; Keirse, Emmanuel; Berghe, Paul Vanden; Beguin, Claire; Desmedt, Marianne; Deveugele, Myriam; Léonard, Christian; Paulus, Dominique; Menten, Johan

2010-11-01

In addition to the effectiveness of hospital care models for terminal patients, policy makers and health care payers are concerned about their costs. This study aims to measure the hospital costs of treating terminal patients in Belgium from the health care payer perspective. Also, this study compares the costs of palliative and usual care in different types of hospital wards. A multicenter, retrospective cohort study compared costs of palliative care with usual care in acute hospital wards and with care in palliative care units. The study enrolled terminal patients from a representative sample of hospitals. Health care costs included fixed hospital costs and charges relating to medical fees, pharmacy and other charges. Data sources consisted of hospital accountancy data and invoice data. Six hospitals participated in the study, generating a total of 146 patients. The findings showed that palliative care in a palliative care unit was more expensive than palliative care in an acute ward due to higher staffing levels in palliative care units. Palliative care in an acute ward is cheaper than usual care in an acute ward. This study suggests that palliative care models in acute wards need to be supported because such care models appear to be less expensive than usual care and because such care models are likely to better reflect the needs of terminal patients. This finding emphasizes the importance of the timely recognition of the need for palliative care in terminal patients treated in acute wards.

Development and Validation of a Practical Two-Step Prediction Model and Clinical Risk Score for Post-Thrombotic Syndrome.

PubMed

Amin, Elham E; van Kuijk, Sander M J; Joore, Manuela A; Prandoni, Paolo; Cate, Hugo Ten; Cate-Hoek, Arina J Ten

2018-06-04

 Post-thrombotic syndrome (PTS) is a common chronic consequence of deep vein thrombosis that affects the quality of life and is associated with substantial costs. In clinical practice, it is not possible to predict the individual patient risk. We develop and validate a practical two-step prediction tool for PTS in the acute and sub-acute phase of deep vein thrombosis.  Multivariable regression modelling with data from two prospective cohorts in which 479 (derivation) and 1,107 (validation) consecutive patients with objectively confirmed deep vein thrombosis of the leg, from thrombosis outpatient clinic of Maastricht University Medical Centre, the Netherlands (derivation) and Padua University hospital in Italy (validation), were included. PTS was defined as a Villalta score of ≥ 5 at least 6 months after acute thrombosis.  Variables in the baseline model in the acute phase were: age, body mass index, sex, varicose veins, history of venous thrombosis, smoking status, provoked thrombosis and thrombus location. For the secondary model, the additional variable was residual vein obstruction. Optimism-corrected area under the receiver operating characteristic curves (AUCs) were 0.71 for the baseline model and 0.60 for the secondary model. Calibration plots showed well-calibrated predictions. External validation of the derived clinical risk scores was successful: AUC, 0.66 (95% confidence interval [CI], 0.63-0.70) and 0.64 (95% CI, 0.60-0.69).  Individual risk for PTS in the acute phase of deep vein thrombosis can be predicted based on readily accessible baseline clinical and demographic characteristics. The individual risk in the sub-acute phase can be predicted with limited additional clinical characteristics. Schattauer GmbH Stuttgart.

Modeling the Urban Boundary and Canopy Layers

EPA Science Inventory

Today, we are confronted with increasingly more sophisticated application requirements for urban modeling. These include those that address emergency response to acute exposures from toxic releases, health exposure assessments from adverse air quality, energy usage, and character...

Time series study of weather, water quality, and acute gastroenteritis at Water Safety Plan implementation sites in France and Spain

PubMed Central

Setty, Karen E.; Enault, Jerome; Loret, Jean-Francois; Serra, Claudia Puigdomenech; Martin-Alonso, Jordi; Bartram, Jamie

2018-01-01

Water Safety Plans (WSPs), recommended by the World Health Organization since 2004, can help drinking water suppliers to proactively identify potential risks and implement preventive barriers that improve safety. Few studies have investigated long-term impacts of WSPs, such as changes in drinking water quality or public health; however, some evidence from high-income countries associates WSP implementation with a reduction in diarrheal disease. To validate the previously observed linkages between WSPs and health outcomes, this time series study examined site-specific relationships between water-related exposures and acute gastroenteritis rates at three locations in France and Spain, including the role of WSP status. Relationships between control or exposure variables and health outcomes were tested using Poisson regression within generalized additive models. Controls included suspected temporal trends in disease reporting. Exposures included temperature, precipitation, raw water quality, and finished water quality (e.g., turbidity, free chlorine). In France, daily acute gastroenteritis cases were tracked using prescription reimbursements; Spanish data aggregated monthly acute gastroenteritis hospital visits. The models identified several significant relationships between indicators of exposure and acute gastroenteritis. Lag times of 6–9 days (including transit time) were most relevant for hydrological indicators (related to precipitation, runoff, and flow) at the two French sites, indicative of viral pathogens. Flush events (defined as surface runoff after a two-week antecedent dry period) linked to nonpoint source pollution were associated with a 10% increase in acute gastroenteritis rates at one location supplied by surface water. Acute gastroenteritis rates were positively associated with elevated turbidity average or maximum values in finished water at locations supplied by both surface and groundwater, by about 4% per 1-NTU increase in the two-week moving average of daily maxima or about 10% per 0.1 NTU increase in the prior month’s average value. In some cases, risk appeared to be mitigated by WSP-related treatment interventions. Our results suggest drinking water exposure is associated with some potentially preventable gastrointestinal illness risk in high-income regions. PMID:29678324

Functional Status Outperforms Comorbidities as a Predictor of 30-Day Acute Care Readmissions in the Inpatient Rehabilitation Population.

PubMed

Shih, Shirley L; Zafonte, Ross; Bates, David W; Gerrard, Paul; Goldstein, Richard; Mix, Jacqueline; Niewczyk, Paulette; Greysen, S Ryan; Kazis, Lewis; Ryan, Colleen M; Schneider, Jeffrey C

2016-10-01

Functional status is associated with patient outcomes, but is rarely included in hospital readmission risk models. The objective of this study was to determine whether functional status is a better predictor of 30-day acute care readmission than traditionally investigated variables including demographics and comorbidities. Retrospective database analysis between 2002 and 2011. 1158 US inpatient rehabilitation facilities. 4,199,002 inpatient rehabilitation facility admissions comprising patients from 16 impairment groups within the Uniform Data System for Medical Rehabilitation database. Logistic regression models predicting 30-day readmission were developed based on age, gender, comorbidities (Elixhauser comorbidity index, Deyo-Charlson comorbidity index, and Medicare comorbidity tier system), and functional status [Functional Independence Measure (FIM)]. We hypothesized that (1) function-based models would outperform demographic- and comorbidity-based models and (2) the addition of demographic and comorbidity data would not significantly enhance function-based models. For each impairment group, Function Only Models were compared against Demographic-Comorbidity Models and Function Plus Models (Function-Demographic-Comorbidity Models). The primary outcome was 30-day readmission, and the primary measure of model performance was the c-statistic. All-cause 30-day readmission rate from inpatient rehabilitation facilities to acute care hospitals was 9.87%. C-statistics for the Function Only Models were 0.64 to 0.70. For all 16 impairment groups, the Function Only Model demonstrated better c-statistics than the Demographic-Comorbidity Models (c-statistic difference: 0.03-0.12). The best-performing Function Plus Models exhibited negligible improvements in model performance compared to Function Only Models, with c-statistic improvements of only 0.01 to 0.05. Readmissions are currently used as a marker of hospital performance, with recent financial penalties to hospitals for excessive readmissions. Function-based readmission models outperform models based only on demographics and comorbidities. Readmission risk models would benefit from the inclusion of functional status as a primary predictor. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Evidence-based Modeling of Critical Illness: An Initial Consensus from the Society for Complexity in Acute Illness

PubMed Central

Vodovotz, Yoram; Clermont, Gilles; Hunt, C. Anthony; Lefering, Rolf; Bartels, John; Seydel, Ruediger; Hotchkiss, John; Ta'asan, Shlomo; Neugebauer, Edmund; An, Gary

2007-01-01

Introduction: Given the complexity of biological systems, understanding their dynamic behaviors, such as the Acute Inflammatory Response (AIR), requires a formal synthetic process. Dynamic Mathematical Modeling (DMM) represents a suite of methods intended for inclusion within the required synthetic framework. DMM, however, is a relatively novel approach in the practice of biomedical research. The Society for Complexity in Acute Illness (SCAI) was formed in 2004 from the leading research groups utilizing DMM in the study of acute inflammation. This Society believes that it is important to offer guidelines for the design, development and utilization of DMM in the setting of AIR research to avoid the “garbage-in garbage-out” problem. Accordingly, SCAI identified a need for and carried out a critical appraisal of DMM as currently used in the setting of acute illness. Methods: The SCAI annual meeting in 2005, the 4th International Conference on Complexity in Acute Illness (ICCAI; Cologne, Germany), was structured with the intent of developing a consensus statement on the methods and execution of DMM in AIR research. The conference was organized to include a series of interactive breakout sessions that included thought leaders from both the DMM and acute illness fields, the results of which were then presented in summary form to the entire group for discussion and consensus. The information in this manuscript represents the concatenation of those presentations. Results: The output from the 4th ICCAI involved consensus statements for the following topics: 1) the need for DMM, 2) a suggested approach for the process of establishing a modeling project, 3) the type of “wet” lab experiments and data needed to establish a modeling project, 4) general quality measures for data to be input to a modeling project, and 5) a descriptive list of several types of DMM to provide guidance in selection of a method for a project. Conclusion: We believe that the complexity of biological systems requires that DMM needs to be among the methods used to improve understanding and make progress with attempts to characterize and manipulate the AIR. We believe that this consensus statement will help guide the integration, rational implementation, and standardization of DMM into general biomedical research. PMID:17371750

Incidence, etiology, and significance of acute kidney injury in the early post-kidney transplant period.

PubMed

Panek, Romuald; Tennankore, Karthik K; Kiberd, Bryce A

2016-01-01

Little is known about the incidence, causes, and significance of acute kidney injury (AKI) in the early transplant period. This study used a definition as >26 μmol/L increase in creatinine within 48 h or >50% increase over a period >48 h. In 326 adult consecutive recipients of a solitary kidney transplant from 2006 to 2014 followed at this center, 21% developed AKI within the first six months. Most etiologies were CNI toxicity (33%) or unknown (26%), whereas acute rejection accounted for 17% and urinary tract obstruction for 10%. Those with AKI had a significantly lower glomerular filtration rate (GFR) at one-yr post-transplant (adjusted beta coefficient -5.5 mL/min/1.73 m(2) , 95% CI: -10.4, -0.7, p = 0.025) in a multivariable linear regression model. However, the AKI definition missed 6 of 19 episodes of acute rejection and 4 of 10 episodes of urinary tract obstruction. When acute rejection (including those that did not satisfy AKI criteria) was included in the model, other causes of AKI were not significantly associated with GFR at year 1. Although AKI, using current criteria, is likely to be a significant predictor of later outcomes, important causes are missed and the criteria are not sensitive for clinical decision-making. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Meta-analysis: Smectite in the treatment of acute infectious diarrhoea in children.

PubMed

Szajewska, H; Dziechciarz, P; Mrukowicz, J

2006-01-15

Although not currently recommended, dioctahedral smectite (smectite) is commonly used to treat acute infectious diarrhoea in many countries. To evaluate systematically the effectiveness of smectite in treating acute infectious diarrhoea in children. Using medical subject headings and free-language terms, the following electronic databases were searched for studies relevant to acute infectious diarrhoea and smectite: MEDLINE, EMBASE, CINAHL and The Cochrane Library; additional references were obtained from reviewed articles. Only randomized-controlled trials were included. Nine randomized-controlled trials (1238 participants) met the inclusion criteria. Combined data from six randomized-controlled trials showed that smectite significantly reduced the duration of diarrhoea compared with placebo. The pooled weighted mean difference was (-22.7 h, 95% CI: -24.8 to -20.6) with a fixed model and remained significant in a random effect model (-24.4 h, 95% CI: -29.8 to -19.1). The chance of cure on intervention day 3 was significantly increased in the smectite vs. the control group (RR 1.64, 95% CI: 1.36-1.98; number needed to treat 4, 95% CI: 3-5). Adverse effects were similar in both groups. Smectite may be a useful adjunct to rehydration therapy in treating acute paediatric gastroenteritis. However, the results of this meta-analysis should be interpreted with caution as most of the included studies had important limitations. Cost-effectiveness analyses should be undertaken before routine pharmacological therapy with smectite is recommended.

Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice.

PubMed

Shafaroodi, Hamed; Shahbek, Farnaz; Faizi, Mehrdad; Ebrahimi, Farzad; Moezi, Leila

2016-01-01

Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington›s disease, amyotrophic lateral sclerosis, as well as Alzheimer›s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more.

Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice

PubMed Central

Shafaroodi, Hamed; Shahbek, Farnaz; Faizi, Mehrdad; Ebrahimi, Farzad; Moezi, Leila

2016-01-01

Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington›s disease, amyotrophic lateral sclerosis, as well as Alzheimer›s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more. PMID:28243281

An evaluation of freshwater mussel toxicity data in the derivation of water quality guidance and standards for copper

USGS Publications Warehouse

March, F.A.; Dwyer, F.J.; Augspurger, T.; Ingersoll, C.G.; Wang, N.; Mebane, C.A.

2007-01-01

The state of Oklahoma has designated several areas as freshwater mussel sanctuaries in an attempt to provide freshwater mussel species a degree of protection and to facilitate their reproduction. We evaluated the protection afforded freshwater mussels by the U.S. Environmental Protection Agency (U.S. EPA) hardness-based 1996 ambient copper water quality criteria, the 2007 U.S. EPA water quality criteria based on the biotic ligand model and the 2005 state of Oklahoma copper water quality standards. Both the criterion maximum concentration and criterion continuous concentration were evaluated. Published acute and chronic copper toxicity data that met American Society for Testing and Materials guidance for test acceptability were obtained for exposures conducted with glochidia or juvenile freshwater mussels. We tabulated toxicity data for glochidia and juveniles to calculate 20 species mean acute values for freshwater mussels. Generally, freshwater mussel species mean acute values were similar to those of the more sensitive species included in the U.S. EPA water quality derivation database. When added to the database of genus mean acute values used in deriving 1996 copper water quality criteria, 14 freshwater mussel genus mean acute values included 10 of the lowest 15 genus mean acute values, with three mussel species having the lowest values. Chronic exposure and sublethal effects freshwater mussel data available for four species and acute to chronic ratios were used to evaluate the criterion continuous concentration. On the basis of the freshwater mussel toxicity data used in this assessment, the hardness-based 1996 U.S. EPA water quality criteria, the 2005 Oklahoma water quality standards, and the 2007 U.S. EPA water quality criteria based on the biotic ligand model might need to be revised to afford protection to freshwater mussels. ?? 2007 SETAC.

A comprehensive approach to improving patient flow in our hospitals--the 'left to right, over and under' concept.

PubMed

Ardagh, Michael

2015-08-21

It is essential we manage the capacity of our hospitals so that acute demand can be accommodated without developing queues for care and backlogs of work. This paper presents a comprehensive model for improving patient flow in our hospitals by attending carefully to both the demand and capacity states of the hospital and maximising efficient flow of our acute patient journeys. The model includes attention to the patient journey as the central focus, with an overarching governance structure and an underpinning sophisticated operations structure.

Pharmacologic therapy for acute pancreatitis

PubMed Central

Kambhampati, Swetha; Park, Walter; Habtezion, Aida

2014-01-01

While conservative management such as fluid, bowel rest, and antibiotics is the mainstay of current acute pancreatitis management, there is a lot of promise in pharmacologic therapies that target various aspects of the pathogenesis of pancreatitis. Extensive review of preclinical studies, which include assessment of therapies such as anti-secretory agents, protease inhibitors, anti-inflammatory agents, and anti-oxidants are discussed. Many of these studies have shown therapeutic benefit and improved survival in experimental models. Based on available preclinical studies, we discuss potential novel targeted pharmacologic approaches that may offer promise in the treatment of acute pancreatitis. To date a variety of clinical studies have assessed the translational potential of animal model effective experimental therapies and have shown either failure or mixed results in human studies. Despite these discouraging clinical studies, there is a great clinical need and there exist several preclinical effective therapies that await investigation in patients. Better understanding of acute pancreatitis pathophysiology and lessons learned from past clinical studies are likely to offer a great foundation upon which to expand future therapies in acute pancreatitis. PMID:25493000

Blood and small intestine cell kinetics under radiation exposures: Mathematical modeling

NASA Astrophysics Data System (ADS)

Smirnova, O. A.

2009-12-01

Mathematical models which describe the dynamics of two vital body systems (hematopoiesis and small intestinal epithelium) in mammals exposed to acute and chronic radiation are developed. These models, based on conventional biological theories, are implemented as systems of nonlinear differential equations. Their variables and constant parameters have clear biological meaning, that provides successful identification and verification of the models in hand. It is shown that the predictions of the models qualitatively and quantitatively agree with the respective experimental data for small laboratory animals (mice, rats) exposed to acute/chronic irradiation in wide ranges of doses and dose rates. The explanation of a number of radiobiological effects, including those of the low-level long-term exposures, is proposed proceeding from the modeling results. All this bears witness to the validity of employment of the developed models, after a proper identification, in investigation and prediction of radiation effects on the hematopoietic and small intestinal epithelium systems in various mammalian species, including humans. In particular, the models can be used for estimating effects of irradiation on astronauts in the long-term space missions, such as Lunar colonies and Mars voyages.

Medicare's post-acute care payment: a review of the issues and policy proposals.

PubMed

Linehan, Kathryn

2012-12-07

Medicare spending on post-acute care provided by skilled nursing facility providers, home health providers, inpatient rehabilitation facility providers, and long-term care hospitals has grown rapidly in the past several years. The Medicare Payment Advisory Commission and others have noted several long-standing problems with the payment systems for post-acute care and have suggested refinements to Medicare's post-acute care payment systems that are intended to encourage the delivery of appropriate care in the right setting for a patient's condition. The Patient Protection and Affordable Care Act of 2010 contained several provisions that affect the Medicare program's post-acute care payment systems and also includes broader payment reforms, such as bundled payment models. This issue brief describes Medicare's payment systems for post-acute care providers, evidence of problems that have been identified with the payment systems, and policies that have been proposed or enacted to remedy those problems.

In Vivo Molecular Imaging of Acute and Subacute Thrombosis Using a Fibrin-Binding Magnetic Resonance Imaging Contrast Agent

PubMed Central

Botnar, René M.; Perez, Alexandra S.; Witte, Sonia; Wiethoff, Andrea J.; Laredo, James; Hamilton, James; Quist, William; Parsons, Edward C.; Vaidya, Anand; Kolodziej, Andrew; Barrett, John A.; Graham, Philip B.; Weisskoff, Robert M.; Manning, Warren J.; Johnstone, Michael T.

2010-01-01

Background Plaque rupture with subsequent thrombosis is recognized as the underlying pathophysiology of most acute coronary syndromes and stroke. Thus, direct thrombus visualization may be beneficial for both diagnosis and guidance of therapy. We sought to test the feasibility of direct imaging of acute and subacute thrombosis using MRI together with a novel fibrin-binding gadolinium-labeled peptide, EP-1873, in an experimental animal model of plaque rupture and thrombosis. Methods and Results Fifteen male New Zealand White rabbits (weight, ≈3.5 kg) were made atherosclerotic by feeding a high-cholesterol diet after endothelial aortic injury. Plaque rupture was then induced with the use of Russell’s viper venom (RVV) and histamine. Subsequently, MRI of the subrenal aorta was performed before RVV, after RVV, and after EP-1873. Histology was performed on regions suggested by MRI to contain thrombus. Nine rabbits (60%) developed plaque rupture and thrombus, including 25 thrombi visually apparent on MRI as “hot spots” after injection of EP-1873. Histological correlation confirmed all 25 thrombi (100%), with no thrombi seen in the other regions of the aorta. In the remaining 6 rabbits (control) without plaque rupture, no thrombus was observed on the MR images or on histology. Conclusions We demonstrate the feasibility of in vivo “molecular” MRI for the detection of acute and subacute thrombosis using a novel fibrin-binding MRI contrast agent in an animal model of atherosclerosis and acute/subacute thrombosis. Potential clinical applications include thrombus detection in acute coronary syndromes and stroke. PMID:15066940

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis.

PubMed

Borer, Luc R; Peel, John E; Seewald, Wolfgang; Schawalder, Peter; Spreng, David E

2003-11-01

To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.

The dynamics of acute inflammation

NASA Astrophysics Data System (ADS)

Kumar, Rukmini

The acute inflammatory response is the non-specific and immediate reaction of the body to pathogenic organisms, tissue trauma and unregulated cell growth. An imbalance in this response could lead to a condition commonly known as "shock" or "sepsis". This thesis is an attempt to elucidate the dynamics of acute inflammatory response to infection and contribute to its systemic understanding through mathematical modeling and analysis. The models of immunity discussed use Ordinary Differential Equations (ODEs) to model the variation of concentration in time of the various interacting species. Chapter 2 discusses three such models of increasing complexity. Sections 2.1 and 2.2 discuss smaller models that capture the core features of inflammation and offer general predictions concerning the design of the system. Phase-space and bifurcation analyses have been used to examine the behavior at various parameter regimes. Section 2.3 discusses a global physiological model that includes several equations modeling the concentration (or numbers) of cells, cytokines and other mediators. The conclusions drawn from the reduced and detailed models about the qualitative effects of the parameters are very similar and these similarities have also been discussed. In Chapter 3, the specific applications of the biologically detailed model are discussed in greater detail. These include a simulation of anthrax infection and an in silico simulation of a clinical trial. Such simulations are very useful to biologists and could prove to be invaluable tools in drug design. Finally, Chapter 4 discusses the general problem of extinction of populations modeled as continuous variables in ODES is discussed. The average time to extinction and threshold are estimated based on analyzing the equivalent stochastic processes.

American Telemedicine Association: Telestroke Guidelines

PubMed Central

Berg, Jill; Chong, Brian W.; Gross, Hartmut; Nystrom, Karin; Adeoye, Opeolu; Schwamm, Lee; Wechsler, Lawrence; Whitchurch, Sallie

2017-01-01

Abstract The following telestroke guidelines were developed to assist practitioners in providing assessment, diagnosis, management, and/or remote consultative support to patients exhibiting symptoms and signs consistent with an acute stroke syndrome, using telemedicine communication technologies. Although telestroke practices may include the more broad utilization of telemedicine across the entire continuum of stroke care, with some even consulting on all neurologic emergencies, this document focuses on the acute phase of stroke, including both pre- and in-hospital encounters for cerebrovascular neurological emergencies. These guidelines describe a network of audiovisual communication and computer systems for delivery of telestroke clinical services and include operations, management, administration, and economic recommendations. These interactive encounters link patients with acute ischemic and hemorrhagic stroke syndromes with acute care facilities with remote and on-site healthcare practitioners providing access to expertise, enhancing clinical practice, and improving quality outcomes and metrics. These guidelines apply specifically to telestroke services and they do not prescribe or recommend overall clinical protocols for stroke patient care. Rather, the focus is on the unique aspects of delivering collaborative bedside and remote care through the telestroke model. PMID:28384077

Acute episodes of predator exposure in conjunction with chronic social instability as an animal model of post-traumatic stress disorder

PubMed Central

Zoladz, Phillip R.; Conrad, Cheryl D.; Fleshner, Monika; Diamond, David M.

2008-01-01

People who are exposed to horrific, life-threatening experiences are at risk for developing post-traumatic stress disorder (PTSD). Some of the symptoms of PTSD include persistent anxiety, exaggerated startle, cognitive impairments and increased sensitivity to yohimbine, an α2-adrenergic receptor antagonist. We have taken into account the conditions known to induce PTSD, as well as factors responsible for long-term maintenance of the disorder, to develop an animal model of PTSD. Adult male Sprague–Dawley rats were administered a total of 31 days of psychosocial stress, composed of acute and chronic components. The acute component was a 1-h stress session (immobilization during cat exposure), which occurred on Days 1 and 11. The chronic component was that on all 31 days the rats were given unstable housing conditions. We found that psychosocially stressed rats had reduced growth rate, reduced thymus weight, increased adrenal gland weight, increased anxiety, an exaggerated startle response, cognitive impairments, greater cardiovascular and corticosterone reactivity to an acute stressor and heightened responsivity to yohimbine. This work demonstrates the effectiveness of acute inescapable episodes of predator exposure administered in conjunction with daily social instability as an animal model of PTSD. PMID:18574787

Examining the Association Between Comorbidity Indexes and Functional Status in Hospitalized Medicare Fee-for-Service Beneficiaries

PubMed Central

Graham, James E.; Resnik, Linda; Karmarkar, Amol M.; Deutsch, Anne; Tan, Alai; Al Snih, Soham; Ottenbacher, Kenneth J.

2016-01-01

Background Medicare data from acute hospitals do not contain information on functional status. This lack of information limits the ability to conduct rehabilitation-related health services research. Objective The purpose of this study was to examine the associations between 5 comorbidity indexes derived from acute care claims data and functional status assessed at admission to an inpatient rehabilitation facility (IRF). Comorbidity indexes included tier comorbidity, Functional Comorbidity Index (FCI), Charlson Comorbidity Index, Elixhauser Comorbidity Index, and Hierarchical Condition Category (HCC). Design This was a retrospective cohort study. Methods Medicare beneficiaries with stroke, lower extremity joint replacement, and lower extremity fracture discharged to an IRF in 2011 were studied (N=105,441). Data from the beneficiary summary file, Medicare Provider Analysis and Review (MedPAR) file, and Inpatient Rehabilitation Facility–Patient Assessment Instrument (IRF-PAI) file were linked. Inpatient rehabilitation facility admission functional status was used as a proxy for acute hospital discharge functional status. Separate linear regression models for each impairment group were developed to assess the relationships between the comorbidity indexes and functional status. Base models included age, sex, race/ethnicity, disability, dual eligibility, and length of stay. Subsequent models included individual comorbidity indexes. Values of variance explained (R2) with each comorbidity index were compared. Results Base models explained 7.7% of the variance in motor function ratings for stroke, 3.8% for joint replacement, and 7.3% for fracture. The R2 increased marginally when comorbidity indexes were added to base models for stroke, joint replacement, and fracture: Charlson Comorbidity Index (0.4%, 0.5%, 0.3%), tier comorbidity (0.2%, 0.6%, 0.5%), FCI (0.4%, 1.2%, 1.6%), Elixhauser Comorbidity Index (1.2%, 1.9%, 3.5%), and HCC (2.2%, 2.1%, 2.8%). Limitation Patients from 3 impairment categories were included in the sample. Conclusions The 5 comorbidity indexes contributed little to predicting functional status. The indexes examined were not useful as proxies for functional status in the acute settings studied. PMID:26564253

Explanatory models and distress in primary caregivers of patients with acute psychotic presentations: A study from South India.

PubMed

Joy, Deepa S; Manoranjitham, S D; Samuel, P; Jacob, K S

2017-11-01

Emotional distress among caregivers of people with mental illness is common, changes overtime and requires appropriate coping strategies to prevent long-term disability. Explanatory models, which underpin understanding of disease and illness, are crucial to coping. To study the association of explanatory models and distress among caregivers of people with acute psychotic illness. A total of 60 consecutive patients and their primary caregivers who presented to the Department of Psychiatry, Christian Medical College, Vellore, were recruited for the study. Positive and Negative Syndrome Scale (PANSS), Short Explanatory Model Interview (SEMI) and the General Health Questionnaire-12 (GHQ-12) were used to assess severity of psychosis, explanatory models of illness and emotional distress. Standard bivariate and multivariable statistics were employed. Majority of the caregivers simultaneously held multiple models of illness, which included medical and non-medical perspectives. The GHQ-12 score were significantly lower in people who held multiple explanatory models of illness when compared to the caregivers who believed single explanations. Explanatory models affect coping in caregivers of patients with acute psychotic presentations. There is a need to have a broad-based approach to recovery and care.

Utility of Immature Granulocyte Percentage in Pediatric Appendicitis

PubMed Central

Mathews, Eleanor K.; Griffin, Russell L.; Mortellaro, Vincent; Beierle, Elizabeth A.; Harmon, Carroll M.; Chen, Mike K.; Russell, Robert T.

2014-01-01

Background Acute appendicitis is the most common cause of abdominal surgery in children. Adjuncts are utilized to help clinicians predict acute or perforated appendicitis, which may affect treatment decisions. Automated hematologic analyzers can perform more accurate automated differentials including immature granulocyte percentages (IG%). Elevated IG% has demonstrated improved accuracy for predicting sepsis in the neonatal population than traditional immature to total neutrophil count (I/T) ratios. We intended to assess the additional discriminatory ability of IG% to traditionally assessed parameters in the differentiation between acute and perforated appendicitis. Materials and Methods We identified all patients with appendicitis from July 2012 to June 2013 by ICD-9 code. Charts were reviewed for relevant demographic, clinical, and outcome data, which were compared between acute and perforated appendicitis groups using Fischer’s exact and t-test for categorical and continuous variables, respectively. We utilized an adjusted logistic regression model utilizing clinical lab values to predict the odds of perforated appendicitis. Results 251 patients were included in the analysis. Those with perforated appendicitis had a higher white blood cell (WBC) count (p=0.0063), C-reactive protein (CRP) (p<0.0001), and IG% (p=0.0299). In the adjusted model, only elevated CRP (OR 3.46, 95% CI 1.40-8.54) and presence of left shift (OR 2.66, 95% CI 1.09-6.46) were significant predictors of perforated appendicitis. The c-statistic of the final model was 0.70, suggesting fair discriminatory ability in predicting perforated appendicitis. Conclusions IG% did not provide any additional benefit to elevated CRP and presence of left shift in the differentiation between acute and perforated appendicitis. PMID:24793450

Models of acute and chronic pancreatitis.

PubMed

Lerch, Markus M; Gorelick, Fred S

2013-06-01

Animal models of acute and chronic pancreatitis have been created to examine mechanisms of pathogenesis, test therapeutic interventions, and study the influence of inflammation on the development of pancreatic cancer. In vitro models can be used to study early stage, short-term processes that involve acinar cell responses. Rodent models reproducibly develop mild or severe disease. One of the most commonly used pancreatitis models is created by administration of supraphysiologic concentrations of caerulein, an ortholog of cholecystokinin. Induction of chronic pancreatitis with factors thought to have a role in human disease, such as combinations of lipopolysaccharide and chronic ethanol feeding, might be relevant to human disease. Models of autoimmune chronic pancreatitis have also been developed. Most models, particularly of chronic pancreatitis, require further characterization to determine which features of human disease they include. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

The second case of a young man with L-arginine-induced acute pancreatitis.

PubMed

Binet, Quentin; Dufour, Inès; Agneessens, Emmanuel; Debongnie, Jean-Claude; Aouattah, Tarik; Covas, Angélique; Coche, Jean-Charles; De Koninck, Xavier

2018-04-21

Dietary supplementation of arginine has been used by numerous world-class athletes and professional bodybuilders over the past 30 years. L-Arginine indeed enhances muscular power and general performance via maintaining ATP level. However, L-arginine is also known to induce acute pancreatitis in murine models. We report the case of young man presenting with upper abdominal pain and increased serum lipase levels. Contrast-enhanced computed tomography confirms a mild acute pancreatitis. Common etiologies have been ruled out and toxicological anamnestic screening reveals the intake of protein powder. This is, to the best of our knowledge, the second case in human of arginine-induced acute pancreatitis. This case report suggests that every patient presenting with acute pancreatitis without obvious etiology should be evaluated for the intake of toxics other than alcohol, including L-arginine.

Medicare Program; Comprehensive Care for Joint Replacement Payment Model for Acute Care Hospitals Furnishing Lower Extremity Joint Replacement Services. Final rule.

PubMed

2015-11-24

This final rule implements a new Medicare Part A and B payment model under section 1115A of the Social Security Act, called the Comprehensive Care for Joint Replacement (CJR) model, in which acute care hospitals in certain selected geographic areas will receive retrospective bundled payments for episodes of care for lower extremity joint replacement (LEJR) or reattachment of a lower extremity. All related care within 90 days of hospital discharge from the joint replacement procedure will be included in the episode of care. We believe this model will further our goals in improving the efficiency and quality of care for Medicare beneficiaries with these common medical procedures.

Optimizing the care model for an uncomplicated acute pain episode in sickle cell disease.

PubMed

Telfer, Paul; Kaya, Banu

2017-12-08

The pathophysiology, clinical presentation, and natural history of acute pain in sickle cell disease are unique and require a disease-centered approach that also applies general principles of acute and chronic pain management. The majority of acute pain episodes are managed at home without the need to access health care. The long-term consequences of poorly treated acute pain include chronic pain, adverse effects of chronic opioid usage, psychological maladjustment, poor quality of life, and excessive health care utilization. There is no standard protocol for management of an acute pain crisis in either the hospital or the community. The assumptions that severe acute pain must be managed in the hospital with parenteral opioids and that strong opioids are needed for home management of pain need to be questioned. Pain management in the emergency department often does not meet acceptable standards, while chronic use of strong opioids is likely to result in opioid-induced hyperalgesia, exacerbation of chronic pain symptoms, and opioid dependency. We suggest that an integrated approach is needed to control the underlying condition, modify psychological responses, optimize social support, and ensure that health care services provide safe, effective, and prompt treatment of acute pain and appropriate management of chronic pain. This integrated approach should begin at an early age and continue through the adolescent, transition, and adult phases of the care model. © 2016 by The American Society of Hematology. All rights reserved.

The Effect of Age on Characteristics and Mortality of Intracerebral Hemorrhage in the Oldest-Old.

PubMed

Forti, Paola; Maioli, Fabiola; Domenico Spampinato, Michele; Barbara, Carlotta; Nativio, Valeria; Coveri, Maura; Zoli, Marco; Simonetti, Luigi; Di Pasquale, Giuseppe; Procaccianti, Gaetano

2016-01-01

Incidence of acute intracerebral hemorrhage (ICH) increases with age, but there is a lack of information about ICH characteristics in the oldest-old (age ≥85 years). In particular, there is a need for information about hematoma volume, which is included in most clinical scales for prediction of mortality in ICH patients. Many of these scales also assume that, independent of ICH characteristics, the oldest-old have a higher mortality than younger elderly patients (age 65-74 years). However, supporting evidence from cohort studies is limited. We investigated ICH characteristics of oldest-old subjects compared to young (<65 years), young-old (65-74 years) and old-old (75-84 years) subjects. We also investigated whether age is an independent mortality predictor in elderly (age ≥65 years) subjects with acute ICH. We retrospectively collected clinical and neuroimaging data of 383 subjects (age 34-104 years) with acute supratentorial primary ICH who were admitted to an Italian Stroke Unit (SU) between October 2007 and December 2014. Measured ICH characteristics included hematoma location, volume and intraventricular extension of hemorrhage on admission CT scan; admission Glasgow Coma Scale ≤8 and hematoma expansion (HE) measured on follow-up CT-scans obtained after 24 h. General linear models and logistic models were used to investigate the association of age with ICH characteristics. These models were adjusted for pre-admission characteristics, hematoma location and time from symptom onset to admission CT scan. Limited to elderly subjects, Cox models were used to investigate the association of age with in-SU and 1-year mortality: the model for in-SU mortality adjusted for pre-admission and ICH admission characteristics and the model for 1-year mortality additionally adjusted for functional status and disposition at SU discharge. Independent of pre-admission characteristics, hematoma location and time from symptom onset to admission CT-scan, oldest-old subjects had the highest admission hematoma volume (p < 0.01). Age was unrelated to all other ICH characteristics including HE. In elderly patients, multivariable adjusted risk of in-SU and 1-year mortality did not vary across age categories. Oldest-old subjects with acute supratentorial ICH have higher admission hematoma volume than young and young-old subjects but do not differ for other ICH characteristics. When taking into account confounding from ICH characteristics, risk of in-SU and 1-year mortality in elderly subjects with acute supratentorial ICH does not differ across age categories. Our findings question use of age as an independent criterion for stratification of mortality risk in elderly subjects with acute ICH. © 2016 S. Karger AG, Basel.

Challenges and Rewards on the Road to Translational Systems Biology in Acute Illness: Four Case Reports from Interdisciplinary Teams

PubMed Central

An, Gary; Hunt, C. Anthony; Clermont, Gilles; Neugebauer, Edmund; Vodovotz, Yoram

2007-01-01

Introduction Translational systems biology approaches can be distinguished from mainstream systems biology in that their goal is to drive novel therapies and streamline clinical trials in critical illness. One systems biology approach, dynamic mathematical modeling (DMM), is increasingly used in dealing with the complexity of the inflammatory response and organ dysfunction. The use of DMM often requires a broadening of research methods and a multidisciplinary team approach that includes bioscientists, mathematicians, engineers, and computer scientists. However, the development of these groups must overcome domain-specific barriers to communication and understanding. Methods We present four case studies of successful translational, interdisciplinary systems biology efforts, which differ by organizational level from an individual to an entire research community. Results Case 1 is a single investigator involved in DMM of the acute inflammatory response at Cook County Hospital, in which extensive translational progress was made using agent-based models of inflammation and organ damage. Case 2 is a community-level effort from the University of Witten-Herdecke in Cologne, whose efforts have led to the formation of the Society for Complexity in Acute Illness. Case 3 is an institution-based group, the Biosystems Group at the University of California, San Francisco, whose work has included a focus on a common lexicon for DMM. Case 4 is an institution-based, trans-disciplinary research group (the Center for Inflammation and Regenerative Modeling at the University of Pittsburgh, whose modeling work has led to internal education efforts, grant support, and commercialization. Conclusion A transdisciplinary approach, which involves team interaction in an iterative fashion to address ambiguity and is supported by educational initiatives, is likely to be necessary for DMM in acute illness. Community-wide organizations such as the Society of Complexity in Acute Illness (SCAI) must strive to facilitate the implementation of DMM in sepsis/trauma research into the research community as a whole. PMID:17548029

Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal

PubMed Central

Cunningham, Christopher L.; Fidler, Tara L.; Murphy, Kevin V.; Mulgrew, Jennifer A.; Smitasin, Phoebe J.

2012-01-01

Background Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Methods Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; non-dependent controls received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. Results The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7-9 h and returning to baseline within 24 h; withdrawal severity was greater in D2 than in B6 mice (Exp. 1). Post-withdrawal delays in initial ethanol access (1, 3 or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (Exp. 2). The post-withdrawal enhancement of ethanol intake persisted over a 5-d abstinence period in D2 mice (Exp. 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than non-dependent mice (Exp. 4). Conclusions Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. PMID:22999529

Adaptation of a Biomarker-Based Sepsis Mortality Risk Stratification Tool for Pediatric Acute Respiratory Distress Syndrome.

PubMed

Yehya, Nadir; Wong, Hector R

2018-01-01

The original Pediatric Sepsis Biomarker Risk Model and revised (Pediatric Sepsis Biomarker Risk Model-II) biomarker-based risk prediction models have demonstrated utility for estimating baseline 28-day mortality risk in pediatric sepsis. Given the paucity of prediction tools in pediatric acute respiratory distress syndrome, and given the overlapping pathophysiology between sepsis and acute respiratory distress syndrome, we tested the utility of Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II for mortality prediction in a cohort of pediatric acute respiratory distress syndrome, with an a priori plan to revise the model if these existing models performed poorly. Prospective observational cohort study. University affiliated PICU. Mechanically ventilated children with acute respiratory distress syndrome. Blood collection within 24 hours of acute respiratory distress syndrome onset and biomarker measurements. In 152 children with acute respiratory distress syndrome, Pediatric Sepsis Biomarker Risk Model performed poorly and Pediatric Sepsis Biomarker Risk Model-II performed modestly (areas under receiver operating characteristic curve of 0.61 and 0.76, respectively). Therefore, we randomly selected 80% of the cohort (n = 122) to rederive a risk prediction model for pediatric acute respiratory distress syndrome. We used classification and regression tree methodology, considering the Pediatric Sepsis Biomarker Risk Model biomarkers in addition to variables relevant to acute respiratory distress syndrome. The final model was comprised of three biomarkers and age, and more accurately estimated baseline mortality risk (area under receiver operating characteristic curve 0.85, p < 0.001 and p = 0.053 compared with Pediatric Sepsis Biomarker Risk Model and Pediatric Sepsis Biomarker Risk Model-II, respectively). The model was tested in the remaining 20% of subjects (n = 30) and demonstrated similar test characteristics. A validated, biomarker-based risk stratification tool designed for pediatric sepsis was adapted for use in pediatric acute respiratory distress syndrome. The newly derived Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model demonstrates good test characteristics internally and requires external validation in a larger cohort. Tools such as Pediatric Acute Respiratory Distress Syndrome Biomarker Risk Model have the potential to provide improved risk stratification and prognostic enrichment for future trials in pediatric acute respiratory distress syndrome.

Development of a prediction tool for patients presenting with acute cough in primary care: a prognostic study spanning six European countries.

PubMed

Bruyndonckx, Robin; Hens, Niel; Verheij, Theo Jm; Aerts, Marc; Ieven, Margareta; Butler, Christopher C; Little, Paul; Goossens, Herman; Coenen, Samuel

2018-05-01

Accurate prediction of the course of an acute cough episode could curb antibiotic overprescribing, but is still a major challenge in primary care. The authors set out to develop a new prediction rule for poor outcome (re-consultation with new or worsened symptoms, or hospital admission) in adults presenting to primary care with acute cough. Data were collected from 2604 adults presenting to primary care with acute cough or symptoms suggestive of lower respiratory tract infection (LRTI) within the Genomics to combat Resistance against Antibiotics in Community-acquired LRTI in Europe (GRACE; www.grace-lrti.org) Network of Excellence. Important signs and symptoms for the new prediction rule were found by combining random forest and logistic regression modelling. Performance to predict poor outcome in acute cough patients was compared with that of existing prediction rules, using the models' area under the receiver operator characteristic curve (AUC), and any improvement obtained by including additional test results (C-reactive protein [CRP], blood urea nitrogen [BUN], chest radiography, or aetiology) was evaluated using the same methodology. The new prediction rule, included the baseline Risk of poor outcome, Interference with daily activities, number of years stopped Smoking (> or <45 years), severity of Sputum, presence of Crackles, and diastolic blood pressure (> or <85 mmHg) (RISSC85). Though performance of RISSC85 was moderate (sensitivity 62%, specificity 59%, positive predictive value 27%, negative predictive value 86%, AUC 0.63, 95% confidence interval [CI] = 0.61 to 0.67), it outperformed all existing prediction rules used today (highest AUC 0.53, 95% CI = 0.51 to 0.56), and could not be significantly improved by including additional test results (highest AUC 0.64, 95% CI = 0.62 to 0.68). The new prediction rule outperforms all existing alternatives in predicting poor outcome in adult patients presenting to primary care with acute cough and could not be improved by including additional test results. © British Journal of General Practice 2018.

Specialized stroke services: a meta-analysis comparing three models of care.

PubMed

Foley, Norine; Salter, Katherine; Teasell, Robert

2007-01-01

Using previously published data, the purpose of this study was to identify and discriminate between three different forms of inpatient stroke care based on timing and duration of treatment and to compare the results of clinically important outcomes. Randomized controlled trials, including a recent review of inpatient stroke unit/rehabilitation care, were identified and grouped into three models of care as follows: (a) acute stroke unit care (patients admitted within 36 h of stroke onset and remaining for up to 2 weeks; n = 5), (b) units combining acute and rehabilitative care (combined; n = 4), and (c) rehabilitation units where patients were transferred onto the service approximately 2 weeks following stroke (post-acute; n = 5). Pooled analyses for the outcomes of mortality, combined death and dependency and length of hospital stay were calculated for each model of care, compared to conventional care. All three models of care were associated with significant reductions in the odds of combined death and dependency; however, acute stroke units were not associated with significant reductions in mortality when this outcome was analyzed separately (OR 0.80; 95% CI: 0.61-1.03). Post-acute stroke units were associated with the greatest reduction in the odds of mortality (OR 0.60; 95% CI: 0.44-0.81). Significant reductions in length of hospital stay were associated with combined stroke units only (weighted mean difference -14 days; 95% CI: -27 to -2). Overall, specialized stroke services were associated with significant reductions in mortality, death and dependency and length of hospital stay although not every model of care was associated with equal benefit.

Chronic and acute effects of stress on energy balance: are there appropriate animal models?

PubMed Central

2014-01-01

Stress activates multiple neural and endocrine systems to allow an animal to respond to and survive in a threatening environment. The corticotropin-releasing factor system is a primary initiator of this integrated response, which includes activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The energetic response to acute stress is determined by the nature and severity of the stressor, but a typical response to an acute stressor is inhibition of food intake, increased heat production, and increased activity with sustained changes in body weight, behavior, and HPA reactivity. The effect of chronic psychological stress is more variable. In humans, chronic stress may cause weight gain in restrained eaters who show increased HPA reactivity to acute stress. This phenotype is difficult to replicate in rodent models where chronic psychological stress is more likely to cause weight loss than weight gain. An exception may be hamsters subjected to repeated bouts of social defeat or foot shock, but the data are limited. Recent reports on the food intake and body composition of subordinate members of group-housed female monkeys indicate that these animals have a similar phenotype to human stress-induced eaters, but there are a limited number of investigators with access to the model. Few stress experiments focus on energy balance, but more information on the phenotype of both humans and animal models during and after exposure to acute or chronic stress may provide novel insight into mechanisms that normally control body weight. PMID:25519732

Medicare Program; Advancing Care Coordination Through Episode Payment Models (EPMs); Cardiac Rehabilitation Incentive Payment Model; and Changes to the Comprehensive Care for Joint Replacement Model (CJR). Final rule.

PubMed

2017-01-03

This final rule implements three new Medicare Parts A and B episode payment models, a Cardiac Rehabilitation (CR) Incentive Payment model and modifications to the existing Comprehensive Care for Joint Replacement model under section 1115A of the Social Security Act. Acute care hospitals in certain selected geographic areas will participate in retrospective episode payment models targeting care for Medicare fee-forservice beneficiaries receiving services during acute myocardial infarction, coronary artery bypass graft, and surgical hip/femur fracture treatment episodes. All related care within 90 days of hospital discharge will be included in the episode of care. We believe these models will further our goals of improving the efficiency and quality of care for Medicare beneficiaries receiving care for these common clinical conditions and procedures.

Social, economic and environmental risk factors for acute lower respiratory infections among children under five years of age in Rwanda.

PubMed

Harerimana, Jean-Modeste; Nyirazinyoye, Leatitia; Thomson, Dana R; Ntaganira, Joseph

2016-01-01

In low and middle-income countries, acute lower respiratory illness is responsible for roughly 1 in every 5 child deaths. Rwanda has made major health system improvements including its community health worker systems, and it is one of the few countries in Africa to meet the 2015 Millennium Development Goals, although prevalence of acute lower respiratory infections (4 %) is similar to other countries in sub-Saharan Africa. This study aims to assess social, economic, and environmental factors associated with acute lower respiratory infections among children under five to inform potential further improvements in the health system. This is a cross-sectional study using data collected from women interviewed in the 2010 DHS about 8,484 surviving children under five. Based on a literature review, we defined 19 health, social, economic, and environmental potential risk factors, tested bivariate associations with acute lower respiratory infections, and advanced variables significant at the 0.1 confidence level to logistic regression modelling. We used manual backward stepwise regression to arrive at a final model. All analyses were performed in Stata v13 and adjusted for complex sample design. The following factors were independently associated with acute lower respiratory infections: child's age, anemia level, and receipt of Vitamin A; household toilet type and residence, and season of interview. In multivariate regression, being in the bottom ten percent of households (OR: 1.27, 95 % CI: 0.85-1.87) or being interviewed during the rainy season (OR: 1.61, 95 % CI: 1.24-2.09) was positively associated with acute lower respiratory infections, while urban residence (OR: 0.58, 95 % CI: 0.38-0.88) and being age 24-59 months versus 0-11 months (OR: 0.53, 95 % CI: 0.40-0.69) was negatively associated with acute lower respiratory infections. Potential areas for intervention including community campaigns about acute lower respiratory infections symptoms and treatment, and continued poverty reduction through rural electrification and modern stove distribution which may reduce use of dirty cooking fuel, improve living conditions, and reduce barriers to health care.

Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy

PubMed Central

McGreevy, Kai; Bottros, Michael M.; Raja, Srinivasa N.

2011-01-01

Chronic pain is the leading cause of disability in the United States. The transition from acute to persistent pain is thought to arise from maladaptive neuroplastic mechanisms involving three intertwined processes, peripheral sensitization, central sensitization, and descending modulation. Strategies aimed at preventing persistent pain may target such processes. Models for studying preventive strategies include persistent post-surgical pain (PPP), persistent post-trauma pain (PTP) and post-herpetic neuralgia (PHN). Such entities allow a more defined acute onset of tissue injury after which study of the long-term effects is more easily examined. In this review, we examine the pathophysiology, epidemiology, risk factors, and treatment strategies for the prevention of chronic pain using these models. Both pharmacological and interventional approaches are described, as well as a discussion of preventive strategies on the horizon. PMID:22102847

Modeling the Risk of Radiation-Induced Acute Esophagitis for Combined Washington University and RTOG Trial 93-11 Lung Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Ellen X.; Bradley, Jeffrey D.; El Naqa, Issam

2012-04-01

Purpose: To construct a maximally predictive model of the risk of severe acute esophagitis (AE) for patients who receive definitive radiation therapy (RT) for non-small-cell lung cancer. Methods and Materials: The dataset includes Washington University and RTOG 93-11 clinical trial data (events/patients: 120/374, WUSTL = 101/237, RTOG9311 = 19/137). Statistical model building was performed based on dosimetric and clinical parameters (patient age, sex, weight loss, pretreatment chemotherapy, concurrent chemotherapy, fraction size). A wide range of dose-volume parameters were extracted from dearchived treatment plans, including Dx, Vx, MOHx (mean of hottest x% volume), MOCx (mean of coldest x% volume), and gEUDmore » (generalized equivalent uniform dose) values. Results: The most significant single parameters for predicting acute esophagitis (RTOG Grade 2 or greater) were MOH85, mean esophagus dose (MED), and V30. A superior-inferior weighted dose-center position was derived but not found to be significant. Fraction size was found to be significant on univariate logistic analysis (Spearman R = 0.421, p < 0.00001) but not multivariate logistic modeling. Cross-validation model building was used to determine that an optimal model size needed only two parameters (MOH85 and concurrent chemotherapy, robustly selected on bootstrap model-rebuilding). Mean esophagus dose (MED) is preferred instead of MOH85, as it gives nearly the same statistical performance and is easier to compute. AE risk is given as a logistic function of (0.0688 Asterisk-Operator MED+1.50 Asterisk-Operator ConChemo-3.13), where MED is in Gy and ConChemo is either 1 (yes) if concurrent chemotherapy was given, or 0 (no). This model correlates to the observed risk of AE with a Spearman coefficient of 0.629 (p < 0.000001). Conclusions: Multivariate statistical model building with cross-validation suggests that a two-variable logistic model based on mean dose and the use of concurrent chemotherapy robustly predicts acute esophagitis risk in combined-data WUSTL and RTOG 93-11 trial datasets.« less

Timing matters: the interval between acute stressors within chronic mild stress modifies behavioral and physiologic stress responses in male rats.

PubMed

Cavigelli, Sonia A; Bao, Alexander D; Bourne, Rebecca A; Caruso, Michael J; Caulfield, Jasmine I; Chen, Mary; Smyth, Joshua M

2018-04-12

Chronic mild stress can lead to negative health outcomes. Frequency, duration, and intensity of acute stressors can affect health-related processes. We tested whether the temporal pattern of daily acute stressors (clustered or dispersed across the day) affects depression-related physiology. We used a rodent model to keep stressor frequency, duration, and intensity constant, and experimentally manipulated the temporal pattern of acute stressors delivered during the active phase of the day. Adult male Sprague-Dawley rats were exposed to one of three chronic mild stress groups: Clustered: stressors that occurred within 1 hour of each other (n = 21), Dispersed: stressors that were spread out across the active phase (n = 21), and Control: no stressors presented (n = 21). Acute mild stressors included noise, strobe lights, novel cage, cage tilt, wet bedding, and water immersion. Depression-related outcomes included: sucrose preference, body weight, circulating glucocorticoid (corticosterone) concentration after a novel acute stressor and during basal morning and evening times, and endotoxin-induced circulating interleukin-6 concentrations. Compared to control rats, those in the Clustered group gained less weight, consumed less sucrose, had a blunted acute corticosterone response, and an accentuated acute interleukin-6 response. Rats in the Dispersed group had an attenuated corticosterone decline during the active period and after an acute stressor compared to the Control group. During a chronic mild stress experience, the temporal distribution of daily acute stressors affected health-related physiologic processes. Regular exposure to daily stressors in rapid succession may predict more depression-related symptoms, whereas exposure to stressors dispersed throughout the day may predict diminished glucocorticoid negative feedback.

Acute methanol toxicity in minipigs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorman, D.C.; Dye, J.A.; Nassise, M.P.

1993-01-01

The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Methanol- andmore » formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuroocular toxicosis.« less

Constitutive activation of MAPK cascade in acute quadriplegic myopathy.

PubMed

Di Giovanni, Simone; Molon, Annamaria; Broccolini, Aldobrando; Melcon, Gisela; Mirabella, Massimiliano; Hoffman, Eric P; Servidei, Serenella

2004-02-01

Acute quadriplegic myopathy (AQM; also called "critical illness myopathy") shows acute muscle wasting and weakness and is experienced by some patients with severe systemic illness, often associated with administration of corticosteroids and/or neuroblocking agents. Key aspects of AQM include muscle atrophy and myofilament loss. Although these features are shared with neurogenic atrophy, myogenic atrophy in AQM appears mechanistically distinct from neurogenic atrophy. Using muscle biopsies from AQM, neurogenic atrophy, and normal controls, we show that both myogenic and neurogenic atrophy share induction of myofiber-specific ubiquitin/proteosome pathways (eg, atrogin-1). However, AQM patient muscle showed a specific strong induction of transforming growth factor (TGF)-beta/MAPK pathways. Atrophic AQM myofibers showed coexpression of TGF-beta receptors, p38 MAPK, c-jun, and c-myc, including phosphorylated active forms, and these same fibers showed apoptotic features. Our data suggest a model of AQM pathogenesis in which stress stimuli (sepsis, corticosteroids, pH imbalance, osmotic imbalance) converge on the TGF-beta pathway in myofibers. The acute stimulation of the TGF-beta/MAPK pathway, coupled with the inactivity-induced atrogin-1/proteosome pathway, leads to the acute muscle loss seen in AQM patients.

Progress in the development of animal models of acute kidney injury and its impact on drug discovery.

PubMed

Sanz, Ana B; Sanchez-Niño, María Dolores; Martín-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrián M

2013-07-01

Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches. The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery. New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.

Acute care patient portals: a qualitative study of stakeholder perspectives on current practices.

PubMed

Collins, Sarah A; Rozenblum, Ronen; Leung, Wai Yin; Morrison, Constance Rc; Stade, Diana L; McNally, Kelly; Bourie, Patricia Q; Massaro, Anthony; Bokser, Seth; Dwyer, Cindy; Greysen, Ryan S; Agarwal, Priyanka; Thornton, Kevin; Dalal, Anuj K

2017-04-01

To describe current practices and stakeholder perspectives of patient portals in the acute care setting. We aimed to: (1) identify key features, (2) recognize challenges, (3) understand current practices for design, configuration, and use, and (4) propose new directions for investigation and innovation. Mixed methods including surveys, interviews, focus groups, and site visits with stakeholders at leading academic medical centers. Thematic analyses to inform development of an explanatory model and recommendations. Site surveys were administered to 5 institutions. Thirty interviews/focus groups were conducted at 4 site visits that included a total of 84 participants. Ten themes regarding content and functionality, engagement and culture, and access and security were identified, from which an explanatory model of current practices was developed. Key features included clinical data, messaging, glossary, patient education, patient personalization and family engagement tools, and tiered displays. Four actionable recommendations were identified by group consensus. Design, development, and implementation of acute care patient portals should consider: (1) providing a single integrated experience across care settings, (2) humanizing the patient-clinician relationship via personalization tools, (3) providing equitable access, and (4) creating a clear organizational mission and strategy to achieve outcomes of interest. Portals should provide a single integrated experience across the inpatient and ambulatory settings. Core functionality includes tools that facilitate communication, personalize the patient, and deliver education to advance safe, coordinated, and dignified patient-centered care. Our findings can be used to inform a "road map" for future work related to acute care patient portals. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Acute graft-versus-host disease: from the bench to the bedside

PubMed Central

Blazar, Bruce R.

2009-01-01

During the past decade, progress in basic immunology has been impressive. In parallel, whereas our understanding of the pathophysiology of acute graft-versus-host disease (GVHD) has greatly improved, so has our knowledge of the complexities of the immune system. Much of the immunobiology of acute GVHD has been gleaned from preclinical models and far less from correlations with clinical observations or therapeutic interventions. In this review, we summarize some of the major advances in GVHD pathophysiology, including the translation of these from the bench to the bedside, and discuss preclinical approaches that warrant further exploration in the clinic. PMID:19713461

Homeostasis alteration within small intestinal mucosa after acute enteral refeeding in total parenteral nutrition mouse model

PubMed Central

Feng, Yongjia; Barrett, Meredith; Hou, Yue; Yoon, Hong Keun; Ochi, Takanori

2015-01-01

Feeding strategies to care for patients who transition from enteral nutrient deprivation while on total parenteral nutrition (TPN) to enteral feedings generally proceed to full enteral nutrition once the gastrointestinal tract recovers; however, an increasing body of literature suggests that a subgroup of patients may actually develop an increased incidence of adverse events, including death. To examine this further, we studied the effects of acute refeeding in a mouse model of TPN. Interestingly, refeeding led to some beneficial effects, including prevention in the decline in intestinal epithelial cell (IEC) proliferation. However, refeeding led to a significant increase in mucosal expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), as well as an upregulation in Toll-like receptor 4 (TLR-4). Refeeding also failed to prevent TPN-associated increases in IEC apoptosis, loss of epithelial barrier function, and failure of the leucine-rich repeat-containing G protein-coupled receptor 5-positive stem cell expression. Transitioning from TPN to enteral feedings led to a partial restoration of the small bowel microbial population. In conclusion, while acute refeeding led to some restoration of normal gastrointestinal physiology, enteral refeeding led to a significant increase in mucosal inflammatory markers and may suggest alternative strategies to enteral refeeding should be considered. PMID:26635320

Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal.

PubMed

Cunningham, Christopher L; Fidler, Tara L; Murphy, Kevin V; Mulgrew, Jennifer A; Smitasin, Phoebe J

2013-02-01

Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; nondependent control animals received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7 to 9 hours and returning to baseline within 24 hours; withdrawal severity was greater in D2 than in B6 mice (experiment 1). Postwithdrawal delays in initial ethanol access (1, 3, or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (experiment 2). The postwithdrawal enhancement of ethanol intake persisted over a 5-day abstinence period in D2 mice (experiment 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than nondependent mice (experiment 4). Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

SPARC (secreted protein acidic and rich in cysteine) knockdown protects mice from acute liver injury by reducing vascular endothelial cell damage

PubMed Central

Peixoto, E; Atorrasagasti, C; Aquino, JB; Militello, R; Bayo, J; Fiore, E; Piccioni, F; Salvatierra, E; Alaniz, L; García, MG; Bataller, R; Corrales, F; Gidekel, M; Podhajcer, O; Colombo, MI; Mazzolini, G

2015-01-01

Secreted protein, acidic and rich in cysteine (SPARC) is involved in many biological process including liver fibrogenesis, but its role in acute liver damage is unknown. To examine the role of SPARC in acute liver injury, we used SPARC knock-out (SPARC−/−) mice. Two models of acute liver damage were used: concanavalin A (Con A) and the agonistic anti-CD95 antibody Jo2. SPARC expression levels were analyzed in liver samples from patients with acute-on-chronic alcoholic hepatitis (AH). SPARC expression is increased on acute-on-chronic AH patients. Knockdown of SPARC decreased hepatic damage in the two models of liver injury. SPARC−/− mice showed a marked reduction in Con A-induced necroinflammation. Infiltration by CD4+ T cells, expression of tumor necrosis factor-α and interleukin-6 and apoptosis were attenuated in SPARC−/− mice. Sinusoidal endothelial cell monolayer was preserved and was less activated in Con A-treated SPARC−/− mice. SPARC knockdown reduced Con A-induced autophagy of cultured human microvascular endothelial cells (HMEC-1). Hepatic transcriptome analysis revealed several gene networks that may have a role in the attenuated liver damaged found in Con A-treated SPARC−/− mice. SPARC has a significant role in the development of Con A-induced severe liver injury. These results suggest that SPARC could represent a therapeutic target in acute liver injury. PMID:25410742

Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-κB activation

PubMed Central

Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

2010-01-01

Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-α-evoked translocation of nuclear factor (NF)-κB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-κB and production of TNF-α in mouse macrophage RAW264·7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-α level and inhibited the LPS-evoked nuclear translocation of NF-κB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS. PMID:20030669

Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-kappaB activation.

PubMed

Tanaka, S; Nishiumi, S; Nishida, M; Mizushina, Y; Kobayashi, K; Masuda, A; Fujita, T; Morita, Y; Mizuno, S; Kutsumi, H; Azuma, T; Yoshida, M

2010-05-01

Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear factor (NF)-kappaB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-alpha level and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS.

Pseudomonas aeruginosa RsmA Plays an Important Role during Murine Infection by Influencing Colonization, Virulence, Persistence, and Pulmonary Inflammation▿

PubMed Central

Mulcahy, Heidi; O'Callaghan, Julie; O'Grady, Eoin P.; Maciá, María D.; Borrell, Nuria; Gómez, Cristina; Casey, Pat G.; Hill, Colin; Adams, Claire; Gahan, Cormac G. M.; Oliver, Antonio; O'Gara, Fergal

2008-01-01

The ability of Pseudomonas aeruginosa to cause a broad range of infections in humans is due, at least in part, to its adaptability and its capacity to regulate the expression of key virulence genes in response to specific environmental conditions. Multiple two-component response regulators have been shown to facilitate rapid responses to these environmental conditions, including the coordinated expression of specific virulence determinants. RsmA is a posttranscriptional regulatory protein which controls the expression of a number of virulence-related genes with relevance for acute and chronic infections. Many membrane-bound sensors, including RetS, LadS, and GacS, are responsible for the reciprocal regulation of genes associated with acute infection and chronic persistence. In P. aeruginosa this is due to sensors influencing the expression of the regulatory RNA RsmZ, with subsequent effects on the level of free RsmA. While interactions between an rsmA mutant and human airway epithelial cells have been examined in vitro, the role of RsmA during infection in vivo has not been determined yet. Here the function of RsmA in both acute and chronic models of infection was examined. The results demonstrate that RsmA is involved in initial colonization and dissemination in a mouse model of acute pneumonia. Furthermore, while loss of RsmA results in reduced colonization during the initial stages of acute infection, the data show that mutation of rsmA ultimately favors chronic persistence and results in increased inflammation in the lungs of infected mice. PMID:18025099

Dose-volume effects for pelvic bone marrow in predicting hematological toxicity in prostate cancer radiotherapy with pelvic node irradiation.

PubMed

Sini, Carla; Fiorino, Claudio; Perna, Lucia; Noris Chiorda, Barbara; Deantoni, Chiara Lucrezia; Bianchi, Marco; Sacco, Vincenzo; Briganti, Alberto; Montorsi, Francesco; Calandrino, Riccardo; Di Muzio, Nadia; Cozzarini, Cesare

2016-01-01

To prospectively identify clinical/dosimetric predictors of acute/late hematologic toxicity (HT) in chemo-naÏve patients treated with whole-pelvis radiotherapy (WPRT) for prostate cancer. Data of 121 patients treated with adjuvant/salvage WPRT were analyzed (static-field IMRT n=19; VMAT/Rapidarc n=57; Tomotherapy n=45). Pelvic bone marrow (BM) was delineated as ilium (IL), lumbosacral, lower and whole pelvis (WP), and the relative DVHs were calculated. HT was graded both according to CTCAE v4.03 and as variation in percentage relative to baseline. Logistic regression was used to analyze association between HT and clinical/DVHs factors. Significant differences (p<0.005) in the DVH of BM volumes between different techniques were found: Tomotherapy was associated with larger volumes receiving low doses (3-20 Gy) and smaller receiving 40-50 Gy. Lower baseline absolute values of WBC, neutrophils and lymphocytes (ALC) predicted acute/late HT (p ⩽ 0.001). Higher BM V40 was associated with higher risk of acute Grade3 (OR=1.018) or late Grade2 lymphopenia (OR=1.005). Two models predicting lymphopenia were developed, both including baseline ALC, and BM WP-V40 (AUC=0.73) and IL-V40+smoking (AUC=0.904) for acute/late respectively. Specific regions of pelvic BM predicting acute/late lymphopenia, a risk factor for viral infections, were identified. The 2-variable models including specific constraints to BM may help reduce HT. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cerebrospinal fluid ferritin and albumin index: potential candidates for scoring system to differentiate between bacterial and viral meningitis in children.

PubMed

Jebamalar, Angelin A; Prabhat; Balakrishnapillai, Agiesh K; Parmeswaran, Narayanan; Dhiman, Pooja; Rajendiran, Soundravally

2016-07-01

To evaluate the diagnostic role of cerebrospinal fluid (CSF) ferritin and albumin index (AI = CSF albumin/serum albumin × 1000) in differentiating acute bacterial meningitis (ABM) from acute viral meningitis (AVM) in children. The study included 42 cases each of ABM and AVM in pediatric age group. Receiver operating characteristic (ROC) analysis was carried out for CSF ferritin and AI. Binary logistic regression was also done. CSF ferritin and AI were found significantly higher in ABM compared to AVM. Model obtained using AI and CSF ferritin along with conventional criteria is better than existing models.

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling

PubMed Central

Dick, Thomas E.; Molkov, Yaroslav I.; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J.; Doyle, John; Scheff, Jeremy D.; Calvano, Steve E.; Androulakis, Ioannis P.; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma. PMID:22783197

Linking Inflammation, Cardiorespiratory Variability, and Neural Control in Acute Inflammation via Computational Modeling.

PubMed

Dick, Thomas E; Molkov, Yaroslav I; Nieman, Gary; Hsieh, Yee-Hsee; Jacono, Frank J; Doyle, John; Scheff, Jeremy D; Calvano, Steve E; Androulakis, Ioannis P; An, Gary; Vodovotz, Yoram

2012-01-01

Acute inflammation leads to organ failure by engaging catastrophic feedback loops in which stressed tissue evokes an inflammatory response and, in turn, inflammation damages tissue. Manifestations of this maladaptive inflammatory response include cardio-respiratory dysfunction that may be reflected in reduced heart rate and ventilatory pattern variabilities. We have developed signal-processing algorithms that quantify non-linear deterministic characteristics of variability in biologic signals. Now, coalescing under the aegis of the NIH Computational Biology Program and the Society for Complexity in Acute Illness, two research teams performed iterative experiments and computational modeling on inflammation and cardio-pulmonary dysfunction in sepsis as well as on neural control of respiration and ventilatory pattern variability. These teams, with additional collaborators, have recently formed a multi-institutional, interdisciplinary consortium, whose goal is to delineate the fundamental interrelationship between the inflammatory response and physiologic variability. Multi-scale mathematical modeling and complementary physiological experiments will provide insight into autonomic neural mechanisms that may modulate the inflammatory response to sepsis and simultaneously reduce heart rate and ventilatory pattern variabilities associated with sepsis. This approach integrates computational models of neural control of breathing and cardio-respiratory coupling with models that combine inflammation, cardiovascular function, and heart rate variability. The resulting integrated model will provide mechanistic explanations for the phenomena of respiratory sinus-arrhythmia and cardio-ventilatory coupling observed under normal conditions, and the loss of these properties during sepsis. This approach holds the potential of modeling cross-scale physiological interactions to improve both basic knowledge and clinical management of acute inflammatory diseases such as sepsis and trauma.

Chronic and acute effects of stress on energy balance: are there appropriate animal models?

PubMed

Harris, Ruth B S

2015-02-15

Stress activates multiple neural and endocrine systems to allow an animal to respond to and survive in a threatening environment. The corticotropin-releasing factor system is a primary initiator of this integrated response, which includes activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The energetic response to acute stress is determined by the nature and severity of the stressor, but a typical response to an acute stressor is inhibition of food intake, increased heat production, and increased activity with sustained changes in body weight, behavior, and HPA reactivity. The effect of chronic psychological stress is more variable. In humans, chronic stress may cause weight gain in restrained eaters who show increased HPA reactivity to acute stress. This phenotype is difficult to replicate in rodent models where chronic psychological stress is more likely to cause weight loss than weight gain. An exception may be hamsters subjected to repeated bouts of social defeat or foot shock, but the data are limited. Recent reports on the food intake and body composition of subordinate members of group-housed female monkeys indicate that these animals have a similar phenotype to human stress-induced eaters, but there are a limited number of investigators with access to the model. Few stress experiments focus on energy balance, but more information on the phenotype of both humans and animal models during and after exposure to acute or chronic stress may provide novel insight into mechanisms that normally control body weight. Copyright © 2015 the American Physiological Society.

Persistent impairment in working memory following severe hyperglycemia in newly diagnosed type 2 diabetes.

PubMed

Cerasuolo, Joseph; Izzo, Anthony

2017-01-01

Acute hyperglycemia has been shown to cause cognitive impairments in animal models. There is growing appreciation of the numerous effects of hyperglycemia on neuronal function as well as blood-brain barrier function. In humans, hypoglycemia is well known to cause cognitive deficits acutely, but hyperglycemia has been less well studied. We present a case of selective neurocognitive deficits in the setting of acute hyperglycemia. A 60-year-old man was admitted to the hospital for an episode of acute hyperglycemia in the setting of newly diagnosed diabetes mellitus precipitated by steroid use. He was managed with insulin therapy and discharged home, and later, presented with complaints of memory impairment. Deficits included impairment in his declarative and working memory, to the point of significant impairment in his overall functioning. The patient had no structural lesions on MRI imaging of the brain or other systemic illnesses to explain his specific deficits. We suggest that his acute hyperglycemia may have caused neurological injury, and may be responsible for our patient's memory complaints. Acute hyperglycemia has been associated with poor outcomes in several different central nervous system injuries including cerebrovascular accident and hypoxic injury.Hyperglycemia is responsible for accumulation of reactive oxygen species in the brain, resulting in advanced glycosylated end products and a proinflammatory response that may lead to cellular injury.Further research is needed to define the impact of both acute and chronic hyperglycemia on cognitive impairment and memory.

Validity of cardiac output measurement by the thermodilution method in the presence of acute tricuspid regurgitation.

PubMed

Boerboom, L E; Kinney, T E; Olinger, G N; Hoffmann, R G

1993-10-01

Evaluation of patients with acute tricuspid insufficiency may include assessment of cardiac output by the thermodilution method. The accuracy of estimates of thermodilution-derived cardiac output in the presence of tricuspid insufficiency has been questioned. This study was designed to determine the validity of the thermodilution technique in a canine model of acute reversible tricuspid insufficiency. Cardiac output as measured by thermodilution and electromagnetic flowmeter was compared at two grades of regurgitation. The relationship between these two methods (thermodilution/electromagnetic) changed significantly from a regression slope of 1.01 +/- 0.18 (mean +/- standard deviation) during control conditions to a slope of 0.86 +/- 0.23 (p < 0.02) during severe regurgitation. No significant change was observed between control and mild regurgitation or between the initial control value and a control measurement repeated after tricuspid insufficiency was reversed at the termination of the study. This study shows that in a canine model of severe acute tricuspid regurgitation the thermodilution method underestimates cardiac output by an amount that is proportional to the level of cardiac output and to the grade of regurgitation.

The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model

PubMed Central

Mercher, Thomas; Raffel, Glen D.; Moore, Sandra A.; Cornejo, Melanie G.; Baudry-Bluteau, Dominique; Cagnard, Nicolas; Jesneck, Jonathan L.; Pikman, Yana; Cullen, Dana; Williams, Ifor R.; Akashi, Koichi; Shigematsu, Hirokazu; Bourquin, Jean-Pierre; Giovannini, Marco; Vainchenker, William; Levine, Ross L.; Lee, Benjamin H.; Bernard, Olivier A.; Gilliland, D. Gary

2009-01-01

Acute megakaryoblastic leukemia (AMKL) is a form of acute myeloid leukemia (AML) associated with a poor prognosis. The genetics and pathophysiology of AMKL are not well understood. We generated a knockin mouse model of the one twenty-two–megakaryocytic acute leukemia (OTT-MAL) fusion oncogene that results from the t(1;22)(p13;q13) translocation specifically associated with a subtype of pediatric AMKL. We report here that OTT-MAL expression deregulated transcriptional activity of the canonical Notch signaling pathway transcription factor recombination signal binding protein for immunoglobulin κ J region (RBPJ) and caused abnormal fetal megakaryopoiesis. Furthermore, cooperation between OTT-MAL and an activating mutation of the thrombopoietin receptor myeloproliferative leukemia virus oncogene (MPL) efficiently induced a short-latency AMKL that recapitulated all the features of human AMKL, including megakaryoblast hyperproliferation and maturation block, thrombocytopenia, organomegaly, and extensive fibrosis. Our results establish that concomitant activation of RBPJ (Notch signaling) and MPL (cytokine signaling) transforms cells of the megakaryocytic lineage and suggest that specific targeting of these pathways could be of therapeutic value for human AMKL. PMID:19287095

Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice

PubMed Central

Kim, Ki Rim; Jeong, Chan-Kwon; Park, Kwang-Kyun; Choi, Jong-Hoon; Park, Jung Han Yoon; Lim, Soon Sung; Chung, Won-Yoon

2010-01-01

The anti-inflammatory activity of licorice (LE) and roated licorice (rLE) extracts determined in the murine phorbol ester-induced acute inflammation model and collagen-induced arthritis (CIA) model of human rheumatoid arthritis. rLE possessed greater activity than LE in inhibiting phorbol ester-induced ear edema. Oral administration of LE or rLE reduced clinical arthritis score, paw swelling, and histopathological changes in a murine CIA. LE and rLE decreased the levels of proinflammatory cytokines in serum and matrix metalloproteinase-3 expression in the joints. Cell proliferation and cytokine secretion in response to type II collagen or lipopolysaccharide stimulation were suppressed in spleen cells from LE or rLE-treated CIA mice. Furthermore, LE and rLE treatment prevented oxidative damages in liver and kidney tissues of CIA mice. Taken together, LE and rLE have benefits in protecting against both acute inflammation and chronic inflammatory conditions including rheumatoid arthritis. rLE may inhibit the acute inflammation more potently than LE. PMID:20300198

Normal tissue complication probability (NTCP) modelling using spatial dose metrics and machine learning methods for severe acute oral mucositis resulting from head and neck radiotherapy.

PubMed

Dean, Jamie A; Wong, Kee H; Welsh, Liam C; Jones, Ann-Britt; Schick, Ulrike; Newbold, Kate L; Bhide, Shreerang A; Harrington, Kevin J; Nutting, Christopher M; Gulliford, Sarah L

2016-07-01

Severe acute mucositis commonly results from head and neck (chemo)radiotherapy. A predictive model of mucositis could guide clinical decision-making and inform treatment planning. We aimed to generate such a model using spatial dose metrics and machine learning. Predictive models of severe acute mucositis were generated using radiotherapy dose (dose-volume and spatial dose metrics) and clinical data. Penalised logistic regression, support vector classification and random forest classification (RFC) models were generated and compared. Internal validation was performed (with 100-iteration cross-validation), using multiple metrics, including area under the receiver operating characteristic curve (AUC) and calibration slope, to assess performance. Associations between covariates and severe mucositis were explored using the models. The dose-volume-based models (standard) performed equally to those incorporating spatial information. Discrimination was similar between models, but the RFCstandard had the best calibration. The mean AUC and calibration slope for this model were 0.71 (s.d.=0.09) and 3.9 (s.d.=2.2), respectively. The volumes of oral cavity receiving intermediate and high doses were associated with severe mucositis. The RFCstandard model performance is modest-to-good, but should be improved, and requires external validation. Reducing the volumes of oral cavity receiving intermediate and high doses may reduce mucositis incidence. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

Disaster metrics: quantification of acute medical disasters in trauma-related multiple casualty events through modeling of the Acute Medical Severity Index.

PubMed

Bayram, Jamil D; Zuabi, Shawki

2012-04-01

The interaction between the acute medical consequences of a Multiple Casualty Event (MCE) and the total medical capacity of the community affected determines if the event amounts to an acute medical disaster. There is a need for a comprehensive quantitative model in MCE that would account for both prehospital and hospital-based acute medical systems, leading to the quantification of acute medical disasters. Such a proposed model needs to be flexible enough in its application to accommodate a priori estimation as part of the decision-making process and a posteriori evaluation for total quality management purposes. The concept proposed by de Boer et al in 1989, along with the disaster metrics quantitative models proposed by Bayram et al on hospital surge capacity and prehospital medical response, were used as theoretical frameworks for a new comprehensive model, taking into account both prehospital and hospital systems, in order to quantify acute medical disasters. A quantitative model called the Acute Medical Severity Index (AMSI) was developed. AMSI is the proportion of the Acute Medical Burden (AMB) resulting from the event, compared to the Total Medical Capacity (TMC) of the community affected; AMSI = AMB/TMC. In this model, AMB is defined as the sum of critical (T1) and moderate (T2) casualties caused by the event, while TMC is a function of the Total Hospital Capacity (THC) and the medical rescue factor (R) accounting for the hospital-based and prehospital medical systems, respectively. Qualitatively, the authors define acute medical disaster as "a state after any type of Multiple Casualty Event where the Acute Medical Burden (AMB) exceeds the Total Medical Capacity (TMC) of the community affected." Quantitatively, an acute medical disaster has an AMSI value of more than one (AMB / TMC > 1). An acute medical incident has an AMSI value of less than one, without the need for medical surge. An acute medical emergency has an AMSI value of less than one with utilization of surge capacity (prehospital or hospital-based). An acute medical crisis has an AMSI value between 0.9 and 1, approaching the threshold for an actual medical disaster. A novel quantitative taxonomy in MCE has been proposed by modeling the Acute Medical Severity Index (AMSI). This model accounts for both hospital and prehospital systems, and quantifies acute medical disasters. Prospective applications of various components of this model are encouraged to further verify its applicability and validity.

Acute moderate exercise improves mnemonic discrimination in young adults.

PubMed

Suwabe, Kazuya; Hyodo, Kazuki; Byun, Kyeongho; Ochi, Genta; Yassa, Michael A; Soya, Hideaki

2017-03-01

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O 2peak ) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Relationship between Acute Phase of Chronic Periodontitis and Meteorological Factors in the Maintenance Phase of Periodontal Treatment: A Pilot Study.

PubMed

Takeuchi, Noriko; Ekuni, Daisuke; Tomofuji, Takaaki; Morita, Manabu

2015-08-05

The acute phase of chronic periodontitis may occur even in patients during supportive periodontal therapy. However, the details are not fully understood. Since the natural environment, including meteorology affects human health, we hypothesized that weather conditions may affect occurrence of acute phase of chronic periodontitis. The aim of this study was to investigate the relationship between weather conditions and acute phase of chronic periodontitis in patients under supportive periodontal therapy. Patients who were diagnosed with acute phase of chronic periodontitis under supportive periodontal therapy during 2011-2013 were selected for this study. We performed oral examinations and collected questionnaires and meteorological data. Of 369 patients who experienced acute phase of chronic periodontitis, 153 had acute phase of chronic periodontitis without direct-triggered episodes. When using the autoregressive integrated moving average model of time-series analysis, the independent covariant of maximum hourly range of barometric pressure, maximum hourly range of temperature, and maximum daily wind speed were significantly associated with occurrence of acute phase of chronic periodontitis (p < 0.05), and 3.1% of the variations in these occurrence over the study period were explained by these factors. Meteorological variables may predict occurrence of acute phase of chronic periodontitis.

Identifying Risk for Acute Kidney Injury in Infants and Children Following Cardiac Arrest.

PubMed

Neumayr, Tara M; Gill, Jeff; Fitzgerald, Julie C; Gazit, Avihu Z; Pineda, Jose A; Berg, Robert A; Dean, J Michael; Moler, Frank W; Doctor, Allan

2017-10-01

Our goal was to identify risk factors for acute kidney injury in children surviving cardiac arrest. Retrospective analysis of a public access dataset. Fifteen children's hospitals associated with the Pediatric Emergency Care Applied Research Network. Two hundred ninety-six subjects between 1 day and 18 years old who experienced in-hospital or out-of-hospital cardiac arrest between July 1, 2003, and December 31, 2004. None. Our primary outcome was development of acute kidney injury as defined by the Acute Kidney Injury Network criteria. An ordinal probit model was developed. We found six critical explanatory variables, including total number of epinephrine doses, postcardiac arrest blood pressure, arrest location, presence of a chronic lung condition, pH, and presence of an abnormal baseline creatinine. Total number of epinephrine doses received as well as rate of epinephrine dosing impacted acute kidney injury risk and severity of acute kidney injury. This study is the first to identify risk factors for acute kidney injury in children after cardiac arrest. Our findings regarding the impact of epinephrine dosing are of particular interest and suggest potential for epinephrine toxicity with regard to acute kidney injury. The ability to identify and potentially modify risk factors for acute kidney injury after cardiac arrest may lead to improved morbidity and mortality in this population.

Acute Moderate Exercise Improves Mnemonic Discrimination in Young Adults

PubMed Central

Suwabe, Kazuya; Hyodo, Kazuki; Byun, Kyeongho; Ochi, Genta; Yassa, Michael A.; Soya, Hideaki

2018-01-01

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O2peak) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. PMID:27997992

Risk of Acute Kidney Injury After Intravenous Contrast Media Administration.

PubMed

Hinson, Jeremiah S; Ehmann, Michael R; Fine, Derek M; Fishman, Elliot K; Toerper, Matthew F; Rothman, Richard E; Klein, Eili Y

2017-05-01

The study objective was to determine whether intravenous contrast administration for computed tomography (CT) is independently associated with increased risk for acute kidney injury and adverse clinical outcomes. This single-center retrospective cohort analysis was performed in a large, urban, academic emergency department with an average census of 62,179 visits per year; 17,934 ED visits for patients who underwent contrast-enhanced, unenhanced, or no CT during a 5-year period (2009 to 2014) were included. The intervention was CT scan with or without intravenous contrast administration. The primary outcome was incidence of acute kidney injury. Secondary outcomes included new chronic kidney disease, dialysis, and renal transplantation at 6 months. Logistic regression modeling and between-groups odds ratios with and without propensity-score matching were used to test for an independent association between contrast administration and primary and secondary outcomes. Treatment decisions, including administration of contrast and intravenous fluids, were examined. Rates of acute kidney injury were similar among all groups. Contrast administration was not associated with increased incidence of acute kidney injury (contrast-induced nephropathy criteria odds ratio=0.96, 95% confidence interval 0.85 to 1.08; and Acute Kidney Injury Network/Kidney Disease Improving Global Outcomes criteria odds ratio=1.00, 95% confidence interval 0.87 to 1.16). This was true in all subgroup analyses regardless of baseline renal function and whether comparisons were made directly or after propensity matching. Contrast administration was not associated with increased incidence of chronic kidney disease, dialysis, or renal transplant at 6 months. Clinicians were less likely to prescribe contrast to patients with decreased renal function and more likely to prescribe intravenous fluids if contrast was administered. In the largest well-controlled study of acute kidney injury following contrast administration in the ED to date, intravenous contrast was not associated with an increased frequency of acute kidney injury. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Art, music, story: The evaluation of a person-centred arts in health programme in an acute care older persons' unit.

PubMed

Ford, Karen; Tesch, Leigh; Dawborn, Jacqueline; Courtney-Pratt, Helen

2018-06-01

To evaluate the impact of an arts in health programme delivered by a specialised artist within an acute older person's unit. Acute hospitals must meet the increasingly complex needs of older people who experience multiple comorbidities, often including cognitive impairment, either directly related to their admission or longer term conditions, including dementia. A focus on physical illness, efficiency and tasks within an acute care environment can all divert attention from the psychosocial well-being of patients. This focus also decreases capacity for person-centred approaches that acknowledge and value the older person, their life story, relationships and the care context. The importance of arts for health and wellness, including responsiveness to individual need, is well established: however, there is little evidence about its effectiveness for older people in acute hospital settings. We report on a collaborative arts in health programme on an acute medical ward for older people. The qualitative study used collaborative enquiry underpinned by a constructivist approach to evaluate an arts programme that involved participatory art-making activities, customised music, song and illustration work, and enlivening the unit environment. Data sources included observation of art activities, semi-structured interviews with patients and family members, and focus groups with staff. Data were transcribed and thematically analysed using a line by line approach. The programme had positive impacts for the environment, patients, families and staff. The environment exhibited changes as a result of programme outputs; patients and families were engaged and enjoyed activities that aided recovery from illness; and staff also enjoyed activities and importantly learnt new ways of working with patients. An acute care arts in health programme is a carefully nuanced programme where the skills of the arts health worker are critical to success. Utilising such skill, continued focus on person-centeredness and openness to creativity demonstrated positive impacts for patients, families, staff and the ward environment. This study affirms the contribution of an arts in health program for older persons in an acute care setting in challenging the dominance of a task based medical model and emphasising person-centred care and outcomes. © 2018 John Wiley & Sons Ltd.

Systemic cytokine response in moribund mice of streptococcal toxic shock syndrome model.

PubMed

Saito, Mitsumasa; Kajiwara, Hideko; Iida, Ken-ichiro; Hoshina, Takayuki; Kusuhara, Koichi; Hara, Toshiro; Yoshida, Shin-ichi

2011-02-01

Streptococcus pyogenes causes severe invasive disease in humans, including streptococcal toxic shock syndrome (STSS). We previously reported a mouse model that is similar to human STSS. When mice were infected intramuscularly with 10(7) CFU of S. pyogenes, all of them survived acute phase of infection. After 20 or more days of infection, a number of them died suddenly accompanied by S. pyogenes bacteremia. We call this phenomenon "delayed death". We analyzed the serum cytokine levels of mice with delayed death, and compared them with those of mice who died in the acute phase of intravenous S. pyogenes infection. The serum levels of TNF-α and IFN-γ in mice of delayed death were more than 100 times higher than those in acute death mice. IL-10 and IL-12, which were not detected in acute death, were also significantly higher in mice of delayed death. IL-6 and MCP-1 (CCL-2) were elevated in both groups of mice. It was noteworthy that not only pro-inflammatory cytokines but also anti-inflammatory cytokines were elevated in delayed death. We also found that intravenous TNF-α injection accelerated delayed death, suggesting that an increase of serum TNF-α induced S. pyogenes bacteremia in our mouse model. Copyright © 2010 Elsevier Ltd. All rights reserved.

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment

PubMed Central

Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.

2013-01-01

Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment.

PubMed

Irimia, Andrei; Goh, S-Y Matthew; Torgerson, Carinna M; Stein, Nathan R; Chambers, Micah C; Vespa, Paul M; Van Horn, John D

2013-10-01

To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. Published by Elsevier B.V.

Surfactant Dysfunction in ARDS and Bronchiolitis is Repaired with Cyclodextrins.

PubMed

Al-Saiedy, Mustafa; Gunasekara, Lasantha; Green, Francis; Pratt, Ryan; Chiu, Andrea; Yang, Ailian; Dennis, John; Pieron, Cora; Bjornson, Candice; Winston, Brent; Amrein, Matthias

2018-03-01

Acute respiratory distress syndrome (ARDS) is caused by many factors including inhalation of toxicants, acute barotrauma, acid aspiration, and burns. Surfactant function is impaired in ARDS and acute airway injury resulting in high surface tension with alveolar and small airway collapse, edema, hypoxemia, and death. In this study, we explore the mechanisms whereby surfactant becomes dysfunctional in ARDS and bronchiolitis and its repair with a cyclodextrin drug that sequesters cholesterol. We used in vitro model systems, a mouse model of ARDS, and samples from patients with acute bronchiolitis. Surface tension was measured by captive bubble surfactometry. Patient samples showed severe surfactant inhibition even in the absence of elevated cholesterol levels. Surfactant was also impaired in ARDS mice where the cholesterol to phospholipid ratio (W/W%) was increased. Methyl-β-cyclodextrin (MβCD) restored surfactant function to normal in both human and animal samples. Model studies showed that the inhibition of surfactant was due to both elevated cholesterol and an interaction between cholesterol and oxidized phospholipids. MβCD was also shown to have anti-inflammatory effects. Inhaled cyclodextrins have potential for the treatment of ARDS. They could be delivered in a portable device carried in combat and used following exposure to toxic gases and fumes or shock secondary to hemorrhage and burns.

Ferret lung transplant: an orthotopic model of obliterative bronchiolitis.

PubMed

Sui, H; Olivier, A K; Klesney-Tait, J A; Brooks, L; Tyler, S R; Sun, X; Skopec, A; Kline, J; Sanchez, P G; Meyerholz, D K; Zavazava, N; Iannettoni, M; Engelhardt, J F; Parekh, K R

2013-02-01

Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3-6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosis-associated occlusion of the bronchiolar airways in all allografts of long-term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long-term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long-term survivors develop histologic changes in the allografts that are hallmarks of OB. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Muscle atrophy and fatty infiltration after an acute rotator cuff repair in a sheep model

PubMed Central

Luan, Tammy; Liu, Xuhui; Easley, Jeremiah T.; Ravishankar, Bharat; Puttlitz, Christian; Feeley, Brian T.

2015-01-01

Summary Introduction rotator cuff tears (RCTs) are the most common tendon injury seen in orthopedic patients. Muscle atrophy and fatty infiltration of the muscle are crucial factors that dictate the outcome following rotator cuff surgery. Though less studied in humans, rotator cuff muscle fibrosis has been seen in animal models as well and may influence outcomes as well. The purpose of this study was to determine if the rotator cuff would develop muscle changes even in the setting of an acute repair in a sheep model. We hypothesized that fatty infiltration and fibrosis would be present even after an acute repair six months after initial surgery. Methods twelve female adult sheep underwent an acute rotator cuff tear and immediate repair on the right shoulder. The left shoulder served as a control and did not undergo a tear or a repair. Six months following acute rotator cuff repairs, sheep muscles were harvested to study atrophy, fatty infiltration, and fibrosis by histological analysis, western blotting, and reverse transcription polymerase chain reaction (RT-PCR). Results the repair group demonstrated an increase expression of muscle atrophy, fatty infiltration, and fibrosis related genes. Significantly increased adipocytes, muscle fatty infiltration, and collagen deposition was observed in rotator cuff muscles in the tendon repair group compared to the control group. Conclusions rotator cuff muscle undergoes degradation changes including fatty infiltration and fibrosis even after the tendons are repair immediately after rupture. Level of Evidence Basic Science Study. PMID:26261789

A review of cognitive therapy in acute medical settings. Part I: therapy model and assessment.

PubMed

Levin, Tomer T; White, Craig A; Kissane, David W

2013-04-01

Although cognitive therapy (CT) has established outpatient utility, there is no integrative framework for using CT in acute medical settings where most psychosomatic medicine (P-M) clinicians practice. Biopsychosocial complexity challenges P-M clinicians who want to use CT as the a priori psychotherapeutic modality. For example, how should clinicians modify the data gathering and formulation process to support CT in acute settings? Narrative review methodology is used to describe the framework for a CT informed interview, formulation, and assessment in acute medical settings. Because this review is aimed largely at P-M trainees and educators, exemplary dialogues model the approach (specific CT strategies for common P-M scenarios appear in the companion article.) Structured data gathering needs to be tailored by focusing on cognitive processes informed by the cognitive hypothesis. Agenda setting, Socratic questioning, and adaptations to the mental state examination are necessary. Specific attention is paid to the CT formulation, Folkman's Cognitive Coping Model, self-report measures, data-driven evaluations, and collaboration (e.g., sharing the formulation with the patient.) Integrative CT-psychopharmacological approaches and the importance of empathy are emphasized. The value of implementing psychotherapy in parallel with data gathering because of time urgency is advocated, but this is a significant departure from usual outpatient approaches in which psychotherapy follows evaluation. This conceptual approach offers a novel integrative framework for using CT in acute medical settings, but future challenges include demonstrating clinical outcomes and training P-M clinicians so as to demonstrate fidelity.

Novel solutions for an old disease: diagnosis of acute appendicitis with random forest, support vector machines, and artificial neural networks.

PubMed

Hsieh, Chung-Ho; Lu, Ruey-Hwa; Lee, Nai-Hsin; Chiu, Wen-Ta; Hsu, Min-Huei; Li, Yu-Chuan Jack

2011-01-01

Diagnosing acute appendicitis clinically is still difficult. We developed random forests, support vector machines, and artificial neural network models to diagnose acute appendicitis. Between January 2006 and December 2008, patients who had a consultation session with surgeons for suspected acute appendicitis were enrolled. Seventy-five percent of the data set was used to construct models including random forest, support vector machines, artificial neural networks, and logistic regression. Twenty-five percent of the data set was withheld to evaluate model performance. The area under the receiver operating characteristic curve (AUC) was used to evaluate performance, which was compared with that of the Alvarado score. Data from a total of 180 patients were collected, 135 used for training and 45 for testing. The mean age of patients was 39.4 years (range, 16-85). Final diagnosis revealed 115 patients with and 65 without appendicitis. The AUC of random forest, support vector machines, artificial neural networks, logistic regression, and Alvarado was 0.98, 0.96, 0.91, 0.87, and 0.77, respectively. The sensitivity, specificity, positive, and negative predictive values of random forest were 94%, 100%, 100%, and 87%, respectively. Random forest performed better than artificial neural networks, logistic regression, and Alvarado. We demonstrated that random forest can predict acute appendicitis with good accuracy and, deployed appropriately, can be an effective tool in clinical decision making. Copyright © 2011 Mosby, Inc. All rights reserved.

No significant impact of Foxf1 siRNA treatment in acute and chronic CCl4 liver injury.

PubMed

Abshagen, Kerstin; Rotberg, Tobias; Genz, Berit; Vollmar, Brigitte

2017-08-01

Chronic liver injury of any etiology is the main trigger of fibrogenic responses and thought to be mediated by hepatic stellate cells. Herein, activating transcription factors like forkhead box f1 are described to stimulate pro-fibrogenic genes in hepatic stellate cells. By using a liver-specific siRNA delivery system (DBTC), we evaluated whether forkhead box f1 siRNA treatment exhibit beneficial effects in murine models of acute and chronic CCl 4 -induced liver injury. Systemic administration of DBTC-forkhead box f1 siRNA in mice was only sufficient to silence forkhead box f1 in acute CCl 4 model, but was not able to attenuate liver injury as measured by liver enzymes and necrotic liver cell area. Therapeutic treatment of mice with DBTC-forkhead box f1 siRNA upon chronic CCl 4 exposition failed to inhibit forkhead box f1 expression and hence lacked to diminish hepatic stellate cells activation or fibrosis development. As a conclusion, DBTC-forkhead box f1 siRNA reduced forkhead box f1 expression in a model of acute but not chronic toxic liver injury and showed no positive effects in either of these mice models. Impact statement As liver fibrosis is a worldwide health problem, antifibrotic therapeutic strategies are urgently needed. Therefore, further developments of new technologies including validation in different experimental models of liver disease are essential. Since activation of hepatic stellate cells is a key event upon liver injury, the activating transcription factor forkhead box f1 (Foxf1) represents a potential target gene. Previously, we evaluated Foxf1 silencing by a liver-specific siRNA delivery system (DBTC), exerting beneficial effects in cholestasis. The present study was designed to confirm the therapeutic potential of Foxf1 siRNA in models of acute and chronic CCl 4 -induced liver injury. DBTC-Foxf1 siRNA was only sufficient to silence Foxf1 in acute CCl 4 model and did not ameliorate liver injury or fibrogenesis. This underlines the significance of the experimental model used. Each model displays specific characteristics in the pathogenic nature, time course and severity of fibrosis and the optimal time point for starting a therapy.

Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury.

PubMed

Majercik, Sarah; Bledsoe, Joseph; Ryser, David; Hopkins, Ramona O; Fair, Joseph E; Brock Frost, R; MacDonald, Joel; Barrett, Ryan; Horn, Susan; Pisani, David; Bigler, Erin D; Gardner, Scott; Stevens, Mark; Larson, Michael J

2017-01-01

Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a level one trauma center. Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor Functional Independence Measure (FIM) scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. The DOI quantitative injury lesion volumes and degree of midline shift were obtained from DOI brain computed tomography scans. A multiple stepwise regression model including 13 independent variables was created. This model was used to predict postrehabilitation outcomes, including FIM scores and ability to return to home. A p value less than 0.05 was considered significant. Ninety-six patients were enrolled in the study. Mean age was 43 ± 21 years, admission Glasgow Coma Score was 8.4 ± 4.8, Injury Severity Score was 24.7 ± 9.9, and head Abbreviated Injury Scale score was 3.73 ± 0.97. Acute hospital LOS was 12.3 ± 8.9 days, and rehabilitation LOS was 15.9 ± 9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p = 0.004) and discharge (p = 0.004) and inversely associated with ability to be discharged to home after rehabilitation (p = 0.006). In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller-injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute injury phase may improve surgeons' ultimate outcome predictions in TBI patients. Prognostic/epidemiologic study, level V.

Volumetric analysis of day of injury computed tomography is associated with rehabilitation outcomes after traumatic brain injury

PubMed Central

Majercik, Sarah; Bledsoe, Joseph; Ryser, David; Hopkins, Ramona O.; Fair, Joseph E.; Frost, R. Brock; MacDonald, Joel; Barrett, Ryan; Horn, Susan; Pisani, David; Bigler, Erin D.; Gardner, Scott; Stevens, Mark; Larson, Michael J.

2016-01-01

Introduction Day-of-injury (DOI) brain lesion volumes in traumatic brain injury (TBI) patients are rarely used to predict long-term outcomes in the acute setting. The purpose of this study was to investigate the relationship between acute brain injury lesion volume and rehabilitation outcomes in patients with TBI at a Level One Trauma Center. Methods Patients with TBI who were admitted to our rehabilitation unit after the acute care trauma service from February 2009-July 2011 were eligible for the study. Demographic data and outcome variables including cognitive and motor FIM scores, length of stay (LOS) in the rehabilitation unit, and ability to return to home were obtained. DOI quantitative injury lesion volumes and degree of midline shift were obtained from day-of-injury (DOI) brain computed tomography (CT) scans. A multiple step-wise regression model including 13 independent variables was created. This model was used to predict post-rehabilitation outcomes, including FIM scores and ability to return to home. P<0.05 was considered significant. Results 96 patients were enrolled in the study. Mean age was 43±21 years, admission Glasgow Coma Score 8.4±4.8, Injury Severity Score 24.7±9.9, and head Abbreviated Injury Scale score 3.73±0.97. Acute hospital length of stay (LOS) was 12.3±8.9 days and rehabilitation LOS was 15.9±9.3 days. Day-of-injury TBI lesion volumes were inversely associated with cognitive FIM scores at rehabilitation admission (p=0.004) and discharge (p=0.004) and inversely associated with ability to be discharged to home after rehabilitation (p=0.006). Conclusion In a cohort of patients with moderate to severe TBI requiring a rehabilitation unit stay after the acute care hospital stay, DOI brain injury lesion volumes are associated with worse cognitive FIM scores at the time of rehabilitation admission and discharge. Smaller injury volumes were associated with eventual discharge to home. Volumetric neuroimaging in the acute injury phase may improve surgeons’ ultimate outcome predictions in TBI patients. Level of Evidence/Study Type Level V, case series, Prognostic/Epidemiological PMID:27805992

Does weather affect daily pain intensity levels in patients with acute low back pain? A prospective cohort study.

PubMed

Duong, Vicky; Maher, Chris G; Steffens, Daniel; Li, Qiang; Hancock, Mark J

2016-05-01

The aim of this study was to investigate the influence of various weather parameters on pain intensity levels in patients with acute low back pain (LBP). We performed a secondary analysis using data from the PACE trial that evaluated paracetamol (acetaminophen) in the treatment of acute LBP. Data on 1604 patients with LBP were included in the analysis. Weather parameters (precipitation, temperature, relative humidity, and air pressure) were obtained from the Australian Bureau of Meteorology. Pain intensity was assessed daily on a 0-10 numerical pain rating scale over a 2-week period. A generalised estimating equation analysis was used to examine the relationship between daily pain intensity levels and weather in three different time epochs (current day, previous day, and change between previous and current days). A second model was adjusted for important back pain prognostic factors. The analysis did not show any association between weather and pain intensity levels in patients with acute LBP in each of the time epochs. There was no change in strength of association after the model was adjusted for prognostic factors. Contrary to common belief, the results demonstrated that the weather parameters of precipitation, temperature, relative humidity, and air pressure did not influence the intensity of pain reported by patients during an episode of acute LBP.

Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

PubMed Central

Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

2013-01-01

ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevents acute pancreatitis by protecting production of ATP

PubMed Central

Mukherjee, Rajarshi; Mareninova, Olga A; Odinokova, Irina V; Huang, Wei; Murphy, John; Chvanov, Michael; Javed, Muhammad A; Wen, Li; Booth, David M; Cane, Matthew C; Awais, Muhammad; Gavillet, Bruno; Pruss, Rebecca M; Schaller, Sophie; Molkentin, Jeffery D; Tepikin, Alexei V; Petersen, Ole H; Pandol, Stephen J; Gukovsky, Ilya; Criddle, David N; Gukovskaya, Anna S

2016-01-01

Objective Acute pancreatitis is caused by toxins that induce acinar cell calcium overload, zymogen activation, cytokine release and cell death, yet is without specific drug therapy. Mitochondrial dysfunction has been implicated but the mechanism not established. Design We investigated the mechanism of induction and consequences of the mitochondrial permeability transition pore (MPTP) in the pancreas using cell biological methods including confocal microscopy, patch clamp technology and multiple clinically representative disease models. Effects of genetic and pharmacological inhibition of the MPTP were examined in isolated murine and human pancreatic acinar cells, and in hyperstimulation, bile acid, alcoholic and choline-deficient, ethionine-supplemented acute pancreatitis. Results MPTP opening was mediated by toxin-induced inositol trisphosphate and ryanodine receptor calcium channel release, and resulted in diminished ATP production, leading to impaired calcium clearance, defective autophagy, zymogen activation, cytokine production, phosphoglycerate mutase 5 activation and necrosis, which was prevented by intracellular ATP supplementation. When MPTP opening was inhibited genetically or pharmacologically, all biochemical, immunological and histopathological responses of acute pancreatitis in all four models were reduced or abolished. Conclusions This work demonstrates the mechanism and consequences of MPTP opening to be fundamental to multiple forms of acute pancreatitis and validates the MPTP as a drug target for this disease. PMID:26071131

Early High-Frequency Oscillatory Ventilation in Pediatric Acute Respiratory Failure. A Propensity Score Analysis.

PubMed

Bateman, Scot T; Borasino, Santiago; Asaro, Lisa A; Cheifetz, Ira M; Diane, Shelley; Wypij, David; Curley, Martha A Q

2016-03-01

The use of high-frequency oscillatory ventilation (HFOV) for acute respiratory failure in children is prevalent despite the lack of efficacy data. To compare the outcomes of patients with acute respiratory failure managed with HFOV within 24-48 hours of endotracheal intubation with those receiving conventional mechanical ventilation (CMV) and/or late HFOV. This is a secondary analysis of data from the RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) study, a prospective cluster randomized clinical trial conducted between 2009 and 2013 in 31 U.S. pediatric intensive care units. Propensity score analysis, including degree of hypoxia in the model, compared the duration of mechanical ventilation and mortality of patients treated with early HFOV matched with those treated with CMV/late HFOV. Among 2,449 subjects enrolled in RESTORE, 353 patients (14%) were ever supported on HFOV, of which 210 (59%) had HFOV initiated within 24-48 hours of intubation. The propensity score model predicting the probability of receiving early HFOV included 1,064 patients (181 early HFOV vs. 883 CMV/late HFOV) with significant hypoxia (oxygenation index ≥ 8). The degree of hypoxia was the most significant contributor to the propensity score model. After adjusting for risk category, early HFOV use was associated with a longer duration of mechanical ventilation (hazard ratio, 0.75; 95% confidence interval, 0.64-0.89; P = 0.001) but not with mortality (odds ratio, 1.28; 95% confidence interval, 0.92-1.79; P = 0.15) compared with CMV/late HFOV. In adjusted models including important oxygenation variables, early HFOV was associated with a longer duration of mechanical ventilation. These analyses make supporting the current approach to HFOV less convincing.

Predicting and evaluation the severity in acute pancreatitis using a new modeling built on body mass index and intra-abdominal pressure.

PubMed

Fei, Yang; Gao, Kun; Tu, Jianfeng; Wang, Wei; Zong, Guang-Quan; Li, Wei-Qin

2017-06-03

Acute pancreatitis (AP) keeps as severe medical diagnosis and treatment problem. Early evaluation for severity and risk stratification in patients with AP is very important. Some scoring system such as acute physiology and chronic health evaluation-II (APACHE-II), the computed tomography severity index (CTSI), Ranson's score and the bedside index of severity of AP (BISAP) have been used, nevertheless, there're a few shortcomings in these methods. The aim of this study was to construct a new modeling including intra-abdominal pressure (IAP) and body mass index (BMI) to evaluate the severity in AP. The study comprised of two independent cohorts of patients with AP, one set was used to develop modeling from Jinling hospital in the period between January 2013 and October 2016, 1073 patients were included in it; another set was used to validate modeling from the 81st hospital in the period between January 2012 and December 2016, 326 patients were included in it. The association between risk factors and severity of AP were assessed by univariable analysis; multivariable modeling was explored through stepwise selection regression. The change in IAP and BMI were combined to generate a regression equation as the new modeling. Statistical indexes were used to evaluate the value of the prediction in the new modeling. Univariable analysis confirmed change in IAP and BMI to be significantly associated with severity of AP. The predict sensitivity, specificity, positive predictive value, negative predictive value and accuracy by the new modeling for severity of AP were 77.6%, 82.6%, 71.9%, 87.5% and 74.9% respectively in the developing dataset. There were significant differences between the new modeling and other scoring systems in these parameters (P < 0.05). In addition, a comparison of the area under receiver operating characteristic curves of them showed a statistically significant difference (P < 0.05). The same results could be found in the validating dataset. A new modeling based on IAP and BMI is more likely to predict the severity of AP. Copyright © 2017. Published by Elsevier Inc.

Cardiac Rehabilitation Following Acute Coronary Syndrome in Women.

PubMed

Bennett, Amanda L; Lavie, Carl J; Grace, Sherry L

2017-08-01

Acute coronary syndrome (ACS) is among the leading burdens of disease among women. It is a significant driver of morbidity and chronically undermines their quality of life. Cardiac rehabilitation (CR) is indicated for ACS patients in clinical practice guidelines, including those specifically for women. CR is a multi-component model of care, proven to reduce mortality and morbidity, including in women. However, women are significantly less likely to be referred to CR by providers, and if they are referred, to enroll and adhere to programs. Reasons include lack of physician encouragement, preference not to feel fatigue and pain, transportation barriers, comorbidities and caregiving obligations. Strategies to mitigate this under-use include systematic early inpatient referral, tailoring programs to meet women's needs and preferences (e.g., offering dance, opportunities for social interaction), and offering non-supervised delivery models. Unfortunately, these strategies are not widely available to women. Given the greater longevity seen in women, the critical role CR plays in augmenting quality of life in this population must be recognized and care providers must do more to facilitate referral to and encourage participating in CR programs.

Antinociceptive effects of hydroalcoholic extract from Euterpe oleracea Mart. (Açaí) in a rodent model of acute and neuropathic pain.

PubMed

Sudo, Roberto T; Neto, Miguel L; Monteiro, Carlos E S; Amaral, Rachel V; Resende, Ângela C; Souza, Pergentino J C; Zapata-Sudo, Gisele; Moura, Roberto S

2015-07-02

Plants rich in flavonoids, such as açaí (Euterpe oleraceae Mart.), can induce antinociception in experimental animals. Here, we tested an extract obtained from the stones of açaí fruits (açaí stone extract, ASE), a native plant from the Amazon region of Brazil, in models of acute/inflammatory and chronic pain. Antinociceptive effects of ASE were evaluated in the hot plate, formalin, acetic acid writhing, carrageenan, and neuropathic pain models, as well as in thermal hyperalgesia and mechanical allodynia models induced by spinal nerve ligation. Antinociceptive activities were modulated by the administration of cholinergic, adrenergic, opioid, and L-arginine-NO antagonists. Oral administration of ASE (30, 100, or 300 mg.kg(-1)) dose-dependently reduced nociceptive responses to acute/inflammatory pain in mice, including thermal hyperalgesia, acetic acid-induced writhing, and carrageenan-induced thermal hyperalgesia. Moreover, ASE reduced the neurogenic and inflammatory phases after intraplantar injection of formalin in mice. The antinociceptive effect of ASE (100 mg · kg(-1)) in a hot plate protocol, was inhibited by pre-treatment with naloxone (1 mg · kg(-1)), atropine (2 mg · kg(-1)), yohimbine (5 mg · kg(-1)), or L-NAME (30 mg · kg(-1)). Furthermore, ASE prevented chronic pain in a rat spinal nerve ligation model, including thermal hyperalgesia and mechanical allodynia. ASE showed significant antinociceptive effect via a multifactorial mechanism of action, indicating that the extract may be useful in the development of new analgesic drugs.

Noninvasive Biomonitoring Approaches to Determine Dosimetry and Risk Following Acute Chemical Exposure: Analysis of Lead or Organophosphate Insecticide in Saliva

DOE Office of Scientific and Technical Information (OSTI.GOV)

Timchalk, Chuck; Poet, Torka S.; Kousba, Ahmed A.

2004-04-01

There is a need to develop approaches for assessing risk associated with acute exposures to a broad-range of chemical agents and to rapidly determine the potential implications to human health. Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants including heavy metals and pesticides. To advance the application of non-invasive biomonitoring a microfluidic/ electrochemical device has also been developed for the analysis of lead (Pb), using square wave anodic stripping voltammetry. Themore » system demonstrates a linear response over a broad concentration range (1 2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb-acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for non-invasive biomonitoring can provide a sensitive, and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these non-invasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for accessing acute exposure and health risk.« less

Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

PubMed

Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

2017-01-01

Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats

PubMed Central

Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

2017-01-01

Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects. PMID:28824301

Comparison of the Mortality Probability Admission Model III, National Quality Forum, and Acute Physiology and Chronic Health Evaluation IV hospital mortality models: implications for national benchmarking*.

PubMed

Kramer, Andrew A; Higgins, Thomas L; Zimmerman, Jack E

2014-03-01

To examine the accuracy of the original Mortality Probability Admission Model III, ICU Outcomes Model/National Quality Forum modification of Mortality Probability Admission Model III, and Acute Physiology and Chronic Health Evaluation IVa models for comparing observed and risk-adjusted hospital mortality predictions. Retrospective paired analyses of day 1 hospital mortality predictions using three prognostic models. Fifty-five ICUs at 38 U.S. hospitals from January 2008 to December 2012. Among 174,001 intensive care admissions, 109,926 met model inclusion criteria and 55,304 had data for mortality prediction using all three models. None. We compared patient exclusions and the discrimination, calibration, and accuracy for each model. Acute Physiology and Chronic Health Evaluation IVa excluded 10.7% of all patients, ICU Outcomes Model/National Quality Forum 20.1%, and Mortality Probability Admission Model III 24.1%. Discrimination of Acute Physiology and Chronic Health Evaluation IVa was superior with area under receiver operating curve (0.88) compared with Mortality Probability Admission Model III (0.81) and ICU Outcomes Model/National Quality Forum (0.80). Acute Physiology and Chronic Health Evaluation IVa was better calibrated (lowest Hosmer-Lemeshow statistic). The accuracy of Acute Physiology and Chronic Health Evaluation IVa was superior (adjusted Brier score = 31.0%) to that for Mortality Probability Admission Model III (16.1%) and ICU Outcomes Model/National Quality Forum (17.8%). Compared with observed mortality, Acute Physiology and Chronic Health Evaluation IVa overpredicted mortality by 1.5% and Mortality Probability Admission Model III by 3.1%; ICU Outcomes Model/National Quality Forum underpredicted mortality by 1.2%. Calibration curves showed that Acute Physiology and Chronic Health Evaluation performed well over the entire risk range, unlike the Mortality Probability Admission Model and ICU Outcomes Model/National Quality Forum models. Acute Physiology and Chronic Health Evaluation IVa had better accuracy within patient subgroups and for specific admission diagnoses. Acute Physiology and Chronic Health Evaluation IVa offered the best discrimination and calibration on a large common dataset and excluded fewer patients than Mortality Probability Admission Model III or ICU Outcomes Model/National Quality Forum. The choice of ICU performance benchmarks should be based on a comparison of model accuracy using data for identical patients.

A taxonomy of nursing care organization models in hospitals

PubMed Central

2012-01-01

Background Over the last decades, converging forces in hospital care, including cost-containment policies, rising healthcare demands and nursing shortages, have driven the search for new operational models of nursing care delivery that maximize the use of available nursing resources while ensuring safe, high-quality care. Little is known, however, about the distinctive features of these emergent nursing care models. This article contributes to filling this gap by presenting a theoretically and empirically grounded taxonomy of nursing care organization models in the context of acute care units in Quebec and comparing their distinctive features. Methods This study was based on a survey of 22 medical units in 11 acute care facilities in Quebec. Data collection methods included questionnaire, interviews, focus groups and administrative data census. The analytical procedures consisted of first generating unit profiles based on qualitative and quantitative data collected at the unit level, then applying hierarchical cluster analysis to the units’ profile data. Results The study identified four models of nursing care organization: two professional models that draw mainly on registered nurses as professionals to deliver nursing services and reflect stronger support to nurses’ professional practice, and two functional models that draw more significantly on licensed practical nurses (LPNs) and assistive staff (orderlies) to deliver nursing services and are characterized by registered nurses’ perceptions that the practice environment is less supportive of their professional work. Conclusions This study showed that medical units in acute care hospitals exhibit diverse staff mixes, patterns of skill use, work environment design, and support for innovation. The four models reflect not only distinct approaches to dealing with the numerous constraints in the nursing care environment, but also different degrees of approximations to an “ideal” nursing professional practice model described by some leaders in the contemporary nursing literature. While the two professional models appear closer to this ideal, the two functional models are farther removed. PMID:22929127

The Association Between Unhealthy Alcohol Use and Acute Care Expenditures in the 30 Days Following Hospital Discharge Among Older Veterans Affairs Patients with a Medical Condition.

PubMed

Chavez, Laura J; Liu, Chuan-Fen; Tefft, Nathan; Hebert, Paul L; Devine, Beth; Bradley, Katharine A

2017-10-01

Hospital readmissions and emergency department (ED) visits within 30 days of discharge are costly. Heavy alcohol use could predict increased risk for post-discharge acute care. This study assessed 30-day acute care utilization and expenditures for different categories of alcohol use. Veterans Affairs (VA) patients age ≥65 years with past-year alcohol screening, hospitalized for a medical condition, were included. VA and Medicare health care utilization data were used. Two-part models adjusted for patient demographics. Among 416,050 hospitalized patients, 25% had 30-day acute care use. Nondrinking patients (n = 267,746) had increased probability of acute care use, mean utilization days, and expenditures (difference of $345; 95% CI $268-$423), relative to low-risk drinkers (n = 105,023). High-risk drinking patients (n = 5,300) had increased probability of acute care use and mean utilization days, but not expenditures. Although these patients did not have greater acute care expenditures than low-risk drinking patients, they may nevertheless be vulnerable to poor post-discharge outcomes.

Fumarylacetoacetate hydrolase deficient pigs are a novel large animal model of metabolic liver disease

PubMed Central

Hickey, Raymond D.; Mao, Shennen A.; Glorioso, Jaime; Lillegard, Joseph B.; Fisher, James E.; Amiot, Bruce; Rinaldo, Piero; Harding, Cary O.; Marler, Ronald; Finegold, Milton J.; Grompe, Markus; Nyberg, Scott L.

2014-01-01

Hereditary tyrosinemia type I (HT1) is caused by deficiency in fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the last step of tyrosine metabolism. The most severe form of the disease presents acutely during infancy, and is characterized by severe liver involvement, most commonly resulting in death if untreated. Generation of FAH+/− pigs was previously accomplished by adeno-associated virus-mediated gene knockout in fibroblasts and somatic cell nuclear transfer. Subsequently, these animals were outbred and crossed to produce the first FAH−/− pigs. FAH-deficiency produced a lethal defect in utero that was corrected by administration of 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione (NTBC) throughout pregnancy. Animals on NTBC were phenotypically normal at birth; however, animals were euthanized approximately four weeks after withdrawal of NTBC due to clinical decline and physical examination findings of severe liver injury and encephalopthy consistent with acute liver failure. Biochemical and histological analyses, characterized by diffuse and severe hepatocellular damage, confirmed the diagnosis of severe liver injury. FAH−/− pigs provide the first genetically engineered large animal model of a metabolic liver disorder. Future applications of FAH−/− pigs include discovery research as a large animal model of HT1 and spontaneous acute liver failure, and preclinical testing of efficacy of liver cell therapies, including transplantation of hepatocytes, liver stem cells, and pluripotent stem cell-derived hepatocytes. PMID:24879068

A Market-Basket Approach to Predict the Acute Aquatic Toxicity of Munitions and Energetic Materials.

PubMed

Burgoon, Lyle D

2016-06-01

An ongoing challenge in chemical production, including the production of insensitive munitions and energetics, is the ability to make predictions about potential environmental hazards early in the process. To address this challenge, a quantitative structure activity relationship model was developed to predict acute fathead minnow toxicity of insensitive munitions and energetic materials. Computational predictive toxicology models like this one may be used to identify and prioritize environmentally safer materials early in their development. The developed model is based on the Apriori market-basket/frequent itemset mining approach to identify probabilistic prediction rules using chemical atom-pairs and the lethality data for 57 compounds from a fathead minnow acute toxicity assay. Lethality data were discretized into four categories based on the Globally Harmonized System of Classification and Labelling of Chemicals. Apriori identified toxicophores for categories two and three. The model classified 32 of the 57 compounds correctly, with a fivefold cross-validation classification rate of 74 %. A structure-based surrogate approach classified the remaining 25 chemicals correctly at 48 %. This result is unsurprising as these 25 chemicals were fairly unique within the larger set.

Estimation of the incubation period of invasive aspergillosis by survival models in acute myeloid leukemia patients.

PubMed

Bénet, Thomas; Voirin, Nicolas; Nicolle, Marie-Christine; Picot, Stephane; Michallet, Mauricette; Vanhems, Philippe

2013-02-01

The duration of the incubation of invasive aspergillosis (IA) remains unknown. The objective of this investigation was to estimate the time interval between aplasia onset and that of IA symptoms in acute myeloid leukemia (AML) patients. A single-centre prospective survey (2004-2009) included all patients with AML and probable/proven IA. Parametric survival models were fitted to the distribution of the time intervals between aplasia onset and IA. Overall, 53 patients had IA after aplasia, with the median observed time interval between the two being 15 days. Based on log-normal distribution, the median estimated IA incubation period was 14.6 days (95% CI; 12.8-16.5 days).

Should there be pediatric neurohospitalists?

PubMed

Nash, Kendall B; Josephson, S Andrew; Sun, Karen; Ferriero, Donna M

2013-03-05

Hospitalist medicine has gown rapidly over the past decade in response to increasing complexity of hospitalized patients, financial pressures, and a national call for improved quality and safety outcomes. An adult neurohospitalist model of care has recently emerged to address these factors and the need for inpatient neurologists who offer expertise and immediate availability for emergent neurologic conditions such as acute stroke and status epilepticus. Similarly, hospitalized children with acute neurologic disorders require a uniquely high level of care, which increasingly cannot be delivered by pediatric neurologists with busy outpatient practices or by pediatric hospitalists without specialized training. This perspective explores the concept of a pediatric neurohospitalist model of care, including the potential impact on quality of care, hospitalization costs, and education.

Dietary and exercise change following acute cardiac syndrome onset: A latent class growth modelling analysis.

PubMed

Bennett, Paul; Gruszczynska, Ewa; Marke, Victoria

2016-10-01

The present study aim determine sub-group trajectories of change on measures of diet and exercise following acute coronary syndrome. 150 participants were assessed in hospital, 1 month and 6 months subsequently on measures including physical activity, diet, illness beliefs, coping and mood. Change trajectories were measured using latent class growth modelling. Multinomial logistic regression was used to predict class membership. These analyses revealed changes in exercise were confined to a sub-group of participants already reporting relatively high exercise levels; those eating less healthily evidenced modest dietary improvements. Coping, gender, depression and perceived control predicted group membership to a modest degree. © The Author(s) 2015.

A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

DTIC Science & Technology

2016-08-01

Acronyms and Symbols ARA Applied Research Associates, Inc. ARS Acute radiation syndrome d Days DE Differential Evolution DTRA Defense Threat...04-08-2016 Technical Report A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures HDTRA1...epithelial cells to acute radiation alone. The model has been modified for improved radiation response, and an addition to the model allows for thermal injury

Blood Pressure May Be Associated with Arterial Collateralization in Anterior Circulation Ischemic Stroke before Acute Reperfusion Therapy.

PubMed

Jiang, Beisi; Churilov, Leonid; Kanesan, Lasheta; Dowling, Richard; Mitchell, Peter; Dong, Qiang; Davis, Stephen; Yan, Bernard

2017-05-01

Leptomeningeal collaterals maintain arterial perfusion in acute arterial occlusion but may fluctuate subject to arterial blood pressure (ABP). We aim to investigate the relationship between ABP and collaterals as assessed by computer tomography (CT) perfusion in acute ischemic stroke. We retrospectively analyzed acute anterior circulation ischemic stroke patients with CT perfusion from 2009 to 2014. Collateral status using relative filling time delay (rFTD) determined by time delay of collateral-derived contrast opacification within the Sylvian fissure, from 0 seconds to unlimited count. The data were analyzed by zero-inflated negative binomial regression model including an appropriate interaction examining in the model in terms of occlusion location and onset-to-CT time (OCT). Two hundred and seventy patients were included. We found that increment of 10 mm Hg in BP, the odds that a patient would have rFTD equal to 0 seconds increased by 27.9% in systolic BP (SBP) ( p =0.001), by 73.9% in diastolic BP (DBP) ( p <0.001) and by 68.5% in mean BP (MBP) ( p <0.001). For patients with rFTD not necessarily equal to 0 seconds, every 10 mm Hg increase in BP, there was a 7% decrease in expected count of seconds for rFTD in SBP ( p =0.002), 10% decrease for rFTD in DBP and 11% decrease for rFTD in MBP. The arterial occlusion location and OCT showed no significant interaction in the BP-rFTD relationship ( p >0.05). In acute ischemic stroke, higher ABP is possibly associated with improved leptomeningeal collaterals as identified by decreased rFTD.

Modeling Acute Health Effects of Astronauts from Exposure to Large Solar Particle Events

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Kim, Myung-Hee Y.; Cucinotta, Francis A.

2011-01-01

In space exploration outside the Earth s geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possible failure of the mission. Acute risks are of special concern during extra-vehicular activities because of the rapid onset of SPE. However, most SPEs will not lead to acute risks but can lead to mission disruption if accurate projection methods are not available. Acute Radiation Sickness (ARS) is a group of clinical syndromes developing acutely (within several seconds to 3 days) after high dose whole-body or significant partial-body ionizing radiation exposures. The manifestation of these syndromes reflects the disturbance of physiological processes of various cellular groups damaged by radiation. Hematopoietic cells, skin, epithelium, intestine, and vascular endothelium are among the most sensitive tissues of human body to ionizing radiation. Most ARS symptoms are directly related to these tissues and other systems (nervous, endocrine, and cardiovascular, etc.) with coupled regulations. Here we report the progress in bio-mathematical models to describe the dose and time-dependent early human responses to ionizing radiation. The responses include lymphocyte depression, granulocyte modulation, fatigue and weakness syndrome, and upper gastrointestinal distress. The modest dose and dose-rates of SPEs are predicted to lead to large sparing of ARS, however detailed experimental data on a range of proton dose-rates for organ doses from 0.5 to 2 Gy is needed to validate the models. We also report on the ARRBOD code that integrates the BRYNTRN and SUMDOSE codes, which are used to estimate the SPE organ doses for astronauts under various space travel scenarios, with our models of ARS. The more recent effort is to provide easy web access to space radiation risk assessment using the ARRBOD code.

PRESYNAPTIC DOPAMINE MODULATION BY STIMULANT SELF ADMINISTRATION

PubMed Central

España, Rodrigo A.; Jones, Sara R.

2013-01-01

The mesolimbic dopamine system is an essential participant in the initiation and modulation of various forms of goal-directed behavior, including drug reinforcement and addiction processes. Dopamine neurotransmission is increased by acute administration of all drugs of abuse, including the stimulants cocaine and amphetamine. Chronic exposure to these drugs via voluntary self-administration provides a model of stimulant abuse that is useful in evaluating potential behavioral and neurochemical adaptations that occur during addiction. This review describes commonly used methodologies to measure dopamine and baseline parameters of presynaptic dopamine regulation, including exocytotic release and reuptake through the dopamine transporter in the nucleus accumbens core, as well as dramatic adaptations in dopamine neurotransmission and drug sensitivity that occur with acute non-contingent and chronic, contingent self-administration of cocaine and amphetamine. PMID:23277050

The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model.

PubMed

Koyner, Jay L; Carey, Kyle A; Edelson, Dana P; Churpek, Matthew M

2018-07-01

To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. Observational cohort study. Tertiary, urban, academic medical center from November 2008 to January 2016. All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. None. Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine-based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted across admission serum creatinine, acute kidney injury severity, and hospital location. Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage 2. The AUC (95% CI) was 0.90 (0.90-0.90) for predicting stage 2 acute kidney injury within 24 hours and 0.87 (0.87-0.87) within 48 hours. The AUC was 0.96 (0.96-0.96) for receipt of renal replacement therapy (n = 821) in the next 48 hours. Accuracy was similar across hospital settings (ICU, wards, and emergency department) and admitting serum creatinine groupings. At a probability threshold of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a specificity of 85% for stage 2 acute kidney injury and predicted the development of stage 2 a median of 41 hours (interquartile range, 12-141 hr) prior to the development of stage 2 acute kidney injury. Readily available electronic health record data can be used to predict impending acute kidney injury prior to changes in serum creatinine with excellent accuracy across different patient locations and admission serum creatinine. Real-time use of this model would allow early interventions for those at high risk of acute kidney injury.

Comprehensive stroke units: a review of comparative evidence and experience.

PubMed

Chan, Daniel K Y; Cordato, Dennis; O'Rourke, Fintan; Chan, Daniel L; Pollack, Michael; Middleton, Sandy; Levi, Chris

2013-06-01

Stroke unit care offers significant benefits in survival and dependency when compared to general medical ward. Most stroke units are either acute or rehabilitation, but comprehensive (combined acute and rehabilitation) model (comprehensive stroke unit) is less common. To examine different levels of evidence of comprehensive stroke unit compared to other organized inpatient stroke care and share local experience of comprehensive stroke units. Cochrane Library and Medline (1980 to December 2010) review of English language articles comparing stroke units to alternative forms of stroke care delivery, different types of stroke unit models, and differences in processes of care within different stroke unit models. Different levels of comparative evidence of comprehensive stroke units to other models of stroke units are collected. There are no randomized controlled trials directly comparing comprehensive stroke units to other stroke unit models (either acute or rehabilitation). Comprehensive stroke units are associated with reduced length of stay and greatest reduction in combined death and dependency in a meta-analysis study when compared to other stroke unit models. Comprehensive stroke units also have better length of stay and functional outcome when compared to acute or rehabilitation stroke unit models in a cross-sectional study, and better length of stay in a 'before-and-after' comparative study. Components of stroke unit care that improve outcome are multifactorial and most probably include early mobilization. A comprehensive stroke unit model has been successfully implemented in metropolitan and rural hospital settings. Comprehensive stroke units are associated with reductions in length of stay and combined death and dependency and improved functional outcomes compared to other stroke unit models. A comprehensive stroke unit model is worth considering as the preferred model of stroke unit care in the planning and delivery of metropolitan and rural stroke services. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

PubMed

Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

2017-10-01

The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

ADVANCIS Score Predicts Acute Kidney Injury After Percutaneous Coronary Intervention for Acute Coronary Syndrome.

PubMed

Fan, Pei-Chun; Chen, Tien-Hsing; Lee, Cheng-Chia; Tsai, Tsung-Yu; Chen, Yung-Chang; Chang, Chih-Hsiang

2018-01-01

Acute kidney injury (AKI), a common and crucial complication of acute coronary syndrome (ACS) after receiving percutaneous coronary intervention (PCI), is associated with increased mortality and adverse outcomes. This study aimed to develop and validate a risk prediction model for incident AKI after PCI for ACS. We included 82,186 patients admitted for ACS and receiving PCI between 1997 and 2011 from the Taiwan National Health Insurance Research Database and randomly divided them into a training cohort (n = 57,630) and validation cohort (n = 24,656) for risk model development and validation, respectively. Risk factor analysis revealed that age, diabetes mellitus, ventilator use, prior AKI, number of intervened vessels, chronic kidney disease (CKD), intra-aortic balloon pump (IABP) use, cardiogenic shock, female sex, prior stroke, peripheral arterial disease, hypertension, and heart failure were significant risk factors for incident AKI after PCI for ACS. The reduced model, ADVANCIS, comprised 8 clinical parameters (age, diabetes mellitus, ventilator use, prior AKI, number of intervened vessels, CKD, IABP use, cardiogenic shock), with a score scale ranging from 0 to 22, and performed comparably with the full model (area under the receiver operating characteristic curve, 87.4% vs 87.9%). An ADVANCIS score of ≥6 was associated with higher in-hospital mortality risk. In conclusion, the ADVANCIS score is a novel, simple, robust tool for predicting the risk of incident AKI after PCI for ACS, and it can aid in risk stratification to monitor patient care.

The role of autophagy in acute brain injury: A state of flux?

PubMed

Wolf, Michael S; Bayır, Hülya; Kochanek, Patrick M; Clark, Robert S B

2018-04-26

It is established that increased autophagy is readily detectable after various types of acute brain injury, including trauma, focal and global cerebral ischemia. What remains controversial, however, is whether this heightened detection of autophagy in brain represents a homeostatic or pathologic process, or an epiphenomenon. The ultimate role of autophagy after acute brain injury likely depends upon: 1) the degree of brain injury and the overall autophagic burden; 2) the capacity of individual cell types to ramp up autophagic flux; 3) the local redox state and signaling of parallel cell death pathways; 4) the capacity to eliminate damage associated molecular patterns and toxic proteins and metabolites both intra- and extracellularly; and 5) the timing of the pro- or anti-autophagic intervention. In this review, we attempt to reconcile conflicting studies that support both a beneficial and detrimental role for autophagy in models of acute brain injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Predicting acute contact toxicity of pesticides in honeybees (Apis mellifera) through a k-nearest neighbor model.

PubMed

Como, F; Carnesecchi, E; Volani, S; Dorne, J L; Richardson, J; Bassan, A; Pavan, M; Benfenati, E

2017-01-01

Ecological risk assessment of plant protection products (PPPs) requires an understanding of both the toxicity and the extent of exposure to assess risks for a range of taxa of ecological importance including target and non-target species. Non-target species such as honey bees (Apis mellifera), solitary bees and bumble bees are of utmost importance because of their vital ecological services as pollinators of wild plants and crops. To improve risk assessment of PPPs in bee species, computational models predicting the acute and chronic toxicity of a range of PPPs and contaminants can play a major role in providing structural and physico-chemical properties for the prioritisation of compounds of concern and future risk assessments. Over the last three decades, scientific advisory bodies and the research community have developed toxicological databases and quantitative structure-activity relationship (QSAR) models that are proving invaluable to predict toxicity using historical data and reduce animal testing. This paper describes the development and validation of a k-Nearest Neighbor (k-NN) model using in-house software for the prediction of acute contact toxicity of pesticides on honey bees. Acute contact toxicity data were collected from different sources for 256 pesticides, which were divided into training and test sets. The k-NN models were validated with good prediction, with an accuracy of 70% for all compounds and of 65% for highly toxic compounds, suggesting that they might reliably predict the toxicity of structurally diverse pesticides and could be used to screen and prioritise new pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

Hawaii Energy Resource Overviews. Volume 4. Impact of geothermal resource development in Hawaii (including air and water quality)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siegel, S.M.; Siegel, B.Z.

1980-06-01

The environmental consequences of natural processes in a volcanic-fumerolic region and of geothermal resource development are presented. These include acute ecological effects, toxic gas emissions during non-eruptive periods, the HGP-A geothermal well as a site-specific model, and the geothermal resources potential of Hawaii. (MHR)

Sleep Deprivation and Neurobehavioral Dynamics

PubMed Central

Basner, Mathias; Rao, Hengyi; Goel, Namni; Dinges, David F.

2013-01-01

Lifestyles involving sleep deprivation are common, despite mounting evidence that both acute total sleep deprivation and chronically restricted sleep degrade neurobehavioral functions associated with arousal, attention, memory and state stability. Current research suggests dynamic differences in the way the central nervous system responds to acute versus chronic sleep restriction, which is reflected in new models of sleep-wake regulation. Chronic sleep restriction likely induces long-term neuromodulatory changes in brain physiology that could explain why recovery from it may require more time than from acute sleep loss. High intraclass correlations in neurobehavioral responses to sleep loss suggest that these trait-like differences are phenotypic and may include genetic components. Sleep deprivation induces changes in brain metabolism and neural activation that involve distributed networks and connectivity. PMID:23523374

Trajectories and Risk Factors for Post-Traumatic Stress Symptoms following Pediatric Concussion.

PubMed

Truss, Katherine; Godfrey, Celia; Takagi, Michael; Babl, Franz E; Bressan, Silvia; Hearps, Stephen; Clarke, Cathriona; Dunne, Kevin; Anderson, Vicki

2017-07-15

A substantial minority of children experience post-traumatic stress symptoms (PTSS) following injury. Research indicates variation in the trajectory of PTSS following pediatric injury, but investigation of PTSS following concussion has assumed homogeneity. This study aimed to identify differential trajectories of PTSS following pediatric concussion and to investigate risk factors, including acute post-concussive symptoms (PCS), associated with these trajectories. A total of 120 children ages 8-18 years reported PTSS for 3 months following concussion diagnosis using the Child PTSD Symptom Scale, with a score of 16 or above indicating probable post-traumatic stress disorder diagnosis. Age, gender, injury mechanism, loss of consciousness, previous concussions, prior hospitalization, prior diagnosis of depression or anxiety, and acute PCS were assessed as risk factors. Data were analyzed using group-based trajectory modeling. Results revealed 16% of children had clinically significant PTSS 2 weeks post-concussion, declining to 10% at 1 month and 6% at 3 months post-injury. Group-based trajectory modeling identified three trajectories of PTSS post-concussion: "resilient" (70%); "recovering" (25%), in which children experienced elevated acute symptoms that declined over time; and "chronic symptomatology" (5%). Due to small size, the chronic group should be interpreted with caution. Higher acute PCS and prior diagnosis of depression or anxiety both significantly increased predicted probability of recovering trajectory group membership. These findings establish that most children are resilient to PTSS following concussion, but that PTSS do occur acutely in a substantial minority of children. The study indicates mental health factors, particularly PTSS, depression, and anxiety, should be considered integral to models of concussion management and treatment.

Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

PubMed

Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

2016-08-01

Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome.

Determining level of care appropriateness in the patient journey from acute care to rehabilitation

PubMed Central

2011-01-01

Background The selection of patients for rehabilitation, and the timing of transfer from acute care, are important clinical decisions that impact on care quality and patient flow. This paper reports utilization review data on inpatients in acute care with stroke, hip fracture or elective joint replacement, and other inpatients referred for rehabilitation. It examines reasons why acute level of care criteria are not met and explores differences in decision making between acute care and rehabilitation teams around patient appropriateness and readiness for transfer. Methods Cohort study of patients in a large acute referral hospital in Australia followed with the InterQual utilization review tool, modified to also include reasons why utilization criteria are not met. Additional data on team decision making about appropriateness for rehabilitation, and readiness for transfer, were collected on a subset of patients. Results There were 696 episodes of care (7189 bed days). Days meeting acute level of care criteria were 56% (stroke, hip fracture and joint replacement patients) and 33% (other patients, from the time of referral). Most inappropriate days in acute care were due to delays in processes/scheduling (45%) or being more appropriate for rehabilitation or lower level of care (30%). On the subset of patients, the acute care team and the utilization review tool deemed patients ready for rehabilitation transfer earlier than the rehabilitation team (means of 1.4, 1.3 and 4.0 days from the date of referral, respectively). From when deemed medically stable for transfer by the acute care team, 28% of patients became unstable. From when deemed stable by the rehabilitation team or utilization review, 9% and 11%, respectively, became unstable. Conclusions A high proportion of patient days did not meet acute level of care criteria, due predominantly to inefficiencies in care processes, or to patients being more appropriate for an alternative level of care, including rehabilitation. The rehabilitation team was the most accurate in determining ongoing medical stability, but at the cost of a longer acute stay. To avoid inpatients remaining in acute care in a state of 'terra nullius', clinical models which provide rehabilitation within acute care, and more efficient movement to a rehabilitation setting, is required. Utilization review could have a decision support role in the determination of medical stability. PMID:22040281

The impact of ocular hemodynamics and intracranial pressure on intraocular pressure during acute gravitational changes.

PubMed

Nelson, Emily S; Mulugeta, Lealem; Feola, Andrew; Raykin, Julia; Myers, Jerry G; Samuels, Brian C; Ethier, C Ross

2017-08-01

Exposure to microgravity causes a bulk fluid shift toward the head, with concomitant changes in blood volume/pressure, and intraocular pressure (IOP). These and other factors, such as intracranial pressure (ICP) changes, are suspected to be involved in the degradation of visual function and ocular anatomical changes exhibited by some astronauts. This is a significant health concern. Here, we describe a lumped-parameter numerical model to simulate volume/pressure alterations in the eye during gravitational changes. The model includes the effects of blood and aqueous humor dynamics, ICP, and IOP-dependent ocular compliance. It is formulated as a series of coupled differential equations and was validated against four existing data sets on parabolic flight, body inversion, and head-down tilt (HDT). The model accurately predicted acute IOP changes in parabolic flight and HDT, and was satisfactory for the more extreme case of inversion. The short-term response to the changing gravitational field was dominated by ocular blood pressures and compliance, while longer-term responses were more dependent on aqueous humor dynamics. ICP had a negligible effect on acute IOP changes. This relatively simple numerical model shows promising predictive capability. To extend the model to more chronic conditions, additional data on longer-term autoregulation of blood and aqueous humor dynamics are needed. NEW & NOTEWORTHY A significant percentage of astronauts present anatomical changes in the posterior eye tissues after spaceflight. Hypothesized increases in ocular blood volume and intracranial pressure (ICP) in space have been considered to be likely factors. In this work, we provide a novel numerical model of the eye that incorporates ocular hemodynamics, gravitational forces, and ICP changes. We find that changes in ocular hemodynamics govern the response of intraocular pressure during acute gravitational change. Copyright © 2017 the American Physiological Society.

Application of physiologically based pharmacokinetic modeling in setting acute exposure guideline levels for methylene chloride.

PubMed

Bos, Peter Martinus Jozef; Zeilmaker, Marco Jacob; van Eijkeren, Jan Cornelis Henri

2006-06-01

Acute exposure guideline levels (AEGLs) are derived to protect the human population from adverse health effects in case of single exposure due to an accidental release of chemicals into the atmosphere. AEGLs are set at three different levels of increasing toxicity for exposure durations ranging from 10 min to 8 h. In the AEGL setting for methylene chloride, specific additional topics had to be addressed. This included a change of relevant toxicity endpoint within the 10-min to 8-h exposure time range from central nervous system depression caused by the parent compound to formation of carboxyhemoglobin (COHb) via biotransformation to carbon monoxide. Additionally, the biotransformation of methylene chloride includes both a saturable step as well as genetic polymorphism of the glutathione transferase involved. Physiologically based pharmacokinetic modeling was considered to be the appropriate tool to address all these topics in an adequate way. Two available PBPK models were combined and extended with additional algorithms for the estimation of the maximum COHb levels. The model was validated and verified with data obtained from volunteer studies. It was concluded that all the mentioned topics could be adequately accounted for by the PBPK model. The AEGL values as calculated with the model were substantiated by experimental data with volunteers and are concluded to be practically applicable.

Interleukin-6 is associated with chronic hyperglycemia and insulin resistance in patients after acute pancreatitis.

PubMed

Gillies, Nicola; Pendharkar, Sayali A; Asrani, Varsha M; Mathew, Juby; Windsor, John A; Petrov, Maxim S

2016-01-01

Diabetes is a pervasive disease, with a mounting prevalence and burden on health care systems. Under this collective term of diabetes falls diabetes after diseases of the exocrine pancreas, a condition which was previously under-recognised and often mislabeled as type 2 diabetes mellitus and is now increasingly acknowledged as a stand-alone entity. However, there is a paucity of clinical studies investigating the underlying pathophysiology of diabetes after acute pancreatitis, the most frequent disease of the pancreas. This study aimed to investigate the role of adipocytokines in glucose metabolism after acute pancreatitis. This was a cross-sectional follow-up study of a patient cohort diagnosed with acute pancreatitis. Fasting venous blood samples were collected to analyse markers of glucose metabolism (fasting blood glucose, haemoglobin A1c, homeostasis model assessment (HOMA-IR) as a measure of insulin resistance) and adypocytokines (adiponectin, interleukin-6, leptin, monocyte chemoattractant protein-1, retinol binding protein-4, resistin, and tumor necrosis factor-α). Participants were categorized into two groups: normoglycemia after acute pancreatitis and chronic hyperglycemia after acute pancreatitis (CHAP). Binary logistic regression and linear regression analyses were used to investigate the association between each of the adipocytokines and markers of glucose metabolism. Potential confounders were adjusted for in multivariate analyses. A total of 83 patients with acute pancreatitis were included, of whom 19 developed CHAP. Interleukin-6 was significantly associated with CHAP in both unadjusted and adjusted models (p = 0.030 and p = 0.018, respectively). Further, it was also significantly associated with HOMA-IR in both unadjusted and adjusted models (p = 0.029 and p = 0.037, respectively). Other adipocytokines were not significantly associated with markers of glucose metabolism. Interleukin-6 appears to be implicated in the development of chronic hyperglycemia and insulin resistance in patients after acute pancreatitis. It may become a potential target in the prevention and early treatment of diabetes after diseases of the exocrine pancreas. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Geometric Image Biomarker Changes of the Parotid Gland Are Associated With Late Xerostomia.

PubMed

van Dijk, Lisanne V; Brouwer, Charlotte L; van der Laan, Hans Paul; Burgerhof, Johannes G M; Langendijk, Johannes A; Steenbakkers, Roel J H M; Sijtsema, Nanna M

2017-12-01

To identify a surrogate marker for late xerostomia 12 months after radiation therapy (Xer 12m ), according to information obtained shortly after treatment. Differences in parotid gland (PG) were quantified in image biomarkers (ΔIBMs) before and 6 weeks after radiation therapy in 107 patients. By performing stepwise forward selection, ΔIBMs that were associated with Xer 12m were selected. Subsequently other variables, such as PG dose and acute xerostomia scores, were added to improve the prediction performance. All models were internally validated. Prediction of Xer 12m based on PG surface reduction (ΔPG-surface) was good (area under the receiver operating characteristic curve, 0.82). Parotid gland dose was related to ΔPG-surface (P<.001, R 2  = 0.27). The addition of acute xerostomia scores to the ΔPG-surface improved the prediction of Xer 12m significantly, and vice versa. The final model including ΔPG-surface and acute xerostomia had outstanding performance in predicting Xer 12m early after radiation therapy (area under the receiver operating characteristic curve, 0.90). Parotid gland surface reduction was associated with late xerostomia. The early posttreatment model with ΔPG-surface and acute xerostomia scores can be considered as a surrogate marker for late xerostomia. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

PubMed

Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

2015-07-01

Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure.

PubMed

Matsue, Yuya; Ter Maaten, Jozine M; Struck, Joachim; Metra, Marco; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; van Veldhuisen, Dirk J; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A

2017-03-01

Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure. The association between pro-ENK and markers of renal function was evaluated in 95 patients with chronic heart failure who underwent renal hemodynamic measurements, including renal blood flow (RBF) and glomerular filtration rate (GFR) with the use of 131 I-Hippuran and 125 I-iothalamate clearances, respectively. The association between pro-ENK and clinical outcome in acute heart failure was assessed in another 1589 patients. Pro-ENK was strongly correlated with both RBF (P < .001) and GFR (P < .001), but not with renal tubular markers. In the acute heart failure cohort, pro-ENK was a predictor of death through 180 days, heart failure rehospitalization through 60 days, and death or cardiovascular or renal rehospitalization through day 60 in univariable analyses, but its predictive value was lost in a multivariable model when other renal markers were entered in the model. In patients with chronic and acute heart failure, pro-ENK is strongly associated with glomerular function, but not with tubular damage. Pro-ENK provides limited prognostic information in patients with acute heart failure on top of established renal markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Probabilistic dietary exposure assessment taking into account variability in both amount and frequency of consumption.

PubMed

Slob, Wout

2006-07-01

Probabilistic dietary exposure assessments that are fully based on Monte Carlo sampling from the raw intake data may not be appropriate. This paper shows that the data should first be analysed by using a statistical model that is able to take the various dimensions of food consumption patterns into account. A (parametric) model is discussed that takes into account the interindividual variation in (daily) consumption frequencies, as well as in amounts consumed. Further, the model can be used to include covariates, such as age, sex, or other individual attributes. Some illustrative examples show how this model may be used to estimate the probability of exceeding an (acute or chronic) exposure limit. These results are compared with the results based on directly counting the fraction of observed intakes exceeding the limit value. This comparison shows that the latter method is not adequate, in particular for the acute exposure situation. A two-step approach for probabilistic (acute) exposure assessment is proposed: first analyse the consumption data by a (parametric) statistical model as discussed in this paper, and then use Monte Carlo techniques for combining the variation in concentrations with the variation in consumption (by sampling from the statistical model). This approach results in an estimate of the fraction of the population as a function of the fraction of days at which the exposure limit is exceeded by the individual.

A probabilistic assessment of health risks associated with short-term exposure to tropospheric ozone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitfield, R.G; Biller, W.F.; Jusko, M.J.

1996-06-01

The work described in this report is part of a larger risk assessment sponsored by the U.S. Environmental Protection Agency. Earlier efforts developed exposure-response relationships for acute health effects among populations engaged in heavy exertion. Those efforts also developed a probabilistic national ambient air quality standards exposure model and a general methodology for integrating probabilistic exposure-response relation- ships and exposure estimates to calculate overall risk results. Recently published data make it possible to model additional health endpoints (for exposure at moderate exertion), including hospital admissions. New air quality and exposure estimates for alternative national ambient air quality standards for ozonemore » are combined with exposure-response models to produce the risk results for hospital admissions and acute health effects. Sample results explain the methodology and introduce risk output formats.« less

Experimental models of hepatotoxicity related to acute liver failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maes, Michaël; Vinken, Mathieu, E-mail: mvinken@vub.ac.be; Jaeschke, Hartmut

Acute liver failure can be the consequence of various etiologies, with most cases arising from drug-induced hepatotoxicity in Western countries. Despite advances in this field, the management of acute liver failure continues to be one of the most challenging problems in clinical medicine. The availability of adequate experimental models is of crucial importance to provide a better understanding of this condition and to allow identification of novel drug targets, testing the efficacy of new therapeutic interventions and acting as models for assessing mechanisms of toxicity. Experimental models of hepatotoxicity related to acute liver failure rely on surgical procedures, chemical exposuremore » or viral infection. Each of these models has a number of strengths and weaknesses. This paper specifically reviews commonly used chemical in vivo and in vitro models of hepatotoxicity associated with acute liver failure. - Highlights: • The murine APAP model is very close to what is observed in patients. • The Gal/ET model is useful to study TNFα-mediated apoptotic signaling mechanisms. • Fas receptor activation is an effective model of apoptosis and secondary necrosis. • The ConA model is a relevant model of auto-immune hepatitis and viral hepatitis. • Multiple time point evaluation needed in experimental models of acute liver injury.« less

Historical Doses from Tritiated Water and Tritiated Hydrogen Gas Released to the Atmosphere from Lawrence Livermore National Laboratory (LLNL). Part 5. Accidental Releases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, S

2007-08-15

Over the course of fifty-three years, LLNL had six acute releases of tritiated hydrogen gas (HT) and one acute release of tritiated water vapor (HTO) that were too large relative to the annual releases to be included as part of the annual releases from normal operations detailed in Parts 3 and 4 of the Tritium Dose Reconstruction (TDR). Sandia National Laboratories/California (SNL/CA) had one such release of HT and one of HTO. Doses to the maximally exposed individual (MEI) for these accidents have been modeled using an equation derived from the time-dependent tritium model, UFOTRI, and parameter values based onmore » expert judgment. All of these acute releases are described in this report. Doses that could not have been exceeded from the large HT releases of 1965 and 1970 were calculated to be 43 {micro}Sv (4.3 mrem) and 120 {micro}Sv (12 mrem) to an adult, respectively. Two published sets of dose predictions for the accidental HT release in 1970 are compared with the dose predictions of this TDR. The highest predicted dose was for an acute release of HTO in 1954. For this release, the dose that could not have been exceeded was estimated to have been 2 mSv (200 mrem), although, because of the high uncertainty about the predictions, the likely dose may have been as low as 360 {micro}Sv (36 mrem) or less. The estimated maximum exposures from the accidental releases were such that no adverse health effects would be expected. Appendix A lists all accidents and large routine puff releases that have occurred at LLNL and SNL/CA between 1953 and 2005. Appendix B describes the processes unique to tritium that must be modeled after an acute release, some of the time-dependent tritium models being used today, and the results of tests of these models.« less

Diminished neutrophil extracellular trap (NET) formation is a novel innate immune deficiency induced by acute ethanol exposure in polymicrobial sepsis, which can be rescued by CXCL1

PubMed Central

Jin, Liliang; Batra, Sanjay

2017-01-01

Polymicrobial sepsis is the result of an exaggerated host immune response to bacterial pathogens. Animal models and human studies demonstrate that alcohol intoxication is a key risk factor for sepsis-induced mortality. Multiple chemokines, such as CXCL1, CXCL2 and CXCL5 are critical for neutrophil recruitment and proper function of neutrophils. However, it is not quite clear the mechanisms by which acute alcohol suppresses immune responses and whether alcohol-induced immunosuppression can be rescued by chemokines. Thus, we assessed whether acute ethanol challenge via gavage diminishes antibacterial host defense in a sepsis model using cecal ligation and puncture (CLP) and whether this immunosuppression can be rescued by exogenous CXCL1. We found acute alcohol intoxication augments mortality and enhances bacterial growth in mice following CLP. Ethanol exposure impairs critical antibacterial functions of mouse and human neutrophils including reactive oxygen species production, neutrophil extracellular trap (NET) formation, and NET-mediated killing in response to both Gram-negative (E. coli) and Gram-positive (Staphylococcus aureus) pathogens. As compared with WT (C57Bl/6) mice, CXCL1 knockout mice display early mortality following acute alcohol exposure followed by CLP. Recombinant CXCL1 (rCXCL1) in acute alcohol challenged CLP mice increases survival, enhances bacterial clearance, improves neutrophil recruitment, and enhances NET formation (NETosis). Recombinant CXCL1 (rCXCL1) administration also augments bacterial killing by alcohol-treated and E. coli- and S. aureus-infected neutrophils. Taken together, our data unveils novel mechanisms underlying acute alcohol-induced dysregulation of the immune responses in polymicrobial sepsis, and CXCL1 is a critical mediator to rescue alcohol-induced immune dysregulation in polymicrobial sepsis. PMID:28922428

Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to Ischemia/Reperfusion Injury and Solid Organ Allotransplantation

PubMed Central

Day, Judy D.; Metes, Diana M.; Vodovotz, Yoram

2015-01-01

A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient’s (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression. PMID:26441988

Clinical prognostic rules for severe acute respiratory syndrome in low- and high-resource settings.

PubMed

Cowling, Benjamin J; Muller, Matthew P; Wong, Irene O L; Ho, Lai-Ming; Lo, Su-Vui; Tsang, Thomas; Lam, Tai Hing; Louie, Marie; Leung, Gabriel M

2006-07-24

An accurate prognostic model for patients with severe acute respiratory syndrome (SARS) could provide a practical clinical decision aid. We developed and validated prognostic rules for both high- and low-resource settings based on data available at the time of admission. We analyzed data on all 1755 and 291 patients with SARS in Hong Kong (derivation cohort) and Toronto (validation cohort), respectively, using a multivariable logistic scoring method with internal and external validation. Scores were assigned on the basis of patient history in a basic model, and a full model additionally incorporated radiological and laboratory results. The main outcome measure was death. Predictors for mortality in the basic model included older age, male sex, and the presence of comorbid conditions. Additional predictors in the full model included haziness or infiltrates on chest radiography, less than 95% oxygen saturation on room air, high lactate dehydrogenase level, and high neutrophil and low platelet counts. The basic model had an area under the receiver operating characteristic (ROC) curve of 0.860 in the derivation cohort, which was maintained on external validation with an area under the ROC curve of 0.882. The full model improved discrimination with areas under the ROC curve of 0.877 and 0.892 in the derivation and validation cohorts, respectively. The model performs well and could be useful in assessing prognosis for patients who are infected with re-emergent SARS.

A model for emergency department end-of-life communications after acute devastating events--part II: moving from resuscitative to end-of-life or palliative treatment.

PubMed

Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

2012-11-01

The model for emergency department (ED) end-of-life communications after acute devastating events addresses decision-making capacity, surrogates, and advance directives, including legal definitions and application of these steps. Part II concerns communications moving from resuscitative to palliative and end-of-life treatments. After completing the steps involved in determining decision-making, emergency physicians (EPs) should consider starting palliative measures versus continuing resuscitative treatment. As communications related to these end-of-life decisions increasingly fall within the scope of emergency medicine (EM) practice, we need to become educated about and comfortable with them. © 2012 by the Society for Academic Emergency Medicine.

Association between presence of pneumonia and pressure ulcer formation following traumatic spinal cord injury.

PubMed

Krishnan, Shilpa; Karg, Patricia E; Boninger, Michael L; Brienza, David M

2017-07-01

To determine if the presence of pneumonia and pressure ulcers are associated in individuals with an acute spinal cord injury during acute care and rehabilitation hospitalizations. Retrospective, secondary analyses of data obtained from the Spinal Cord Injury Model Systems enrolled from 1993 until 2006 Setting: Acute care hospitalization and inpatient rehabilitation facilities Participants: A cohort of individuals hospitalized in acute care (n = 3,098) and inpatient rehabilitation (n = 1,768) was included in the analysis. Frequencies of pressure ulcer formation and episodes of pneumonia were noted in both settings. Not applicable. Pressure ulcer formation and diagnosis of pneumonia Results: The development of pressure ulcers, including stage I, was 20.3% acute care and 21.1% during in inpatient rehabilitation. Multivariate logistic regression analyses revealed a significant association of pneumonia with occurrence of pressure ulcers (P ≤ 0.001, OR = 2.3 and 2.2 respectively), the American Spinal Injury Association Impairment Scale grades (P < 0.001), and utilization of mechanical ventilation (P < 0.01) in both settings. A higher presence of pressure ulcers was found in individuals with pneumonia, after adjusting for injury severity, age, sex, and utilization of mechanical ventilation. Impaired inflammatory response and decreased mobility in individuals with pneumonia may predispose these individuals to develop pressure ulcers. Surveillance and preventive measures for pressure ulcers should be rigorous in individuals with SCI and pneumonia.

Diabetes, insulin, and development of acute lung injury

PubMed Central

Honiden, Shyoko; Gong, Michelle N.

2009-01-01

Objectives Recently, many studies have investigated the immunomodulatory effects of insulin and glucose control in critical illness. This review examines evidence regarding the relationship between diabetes and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), reviews studies of lung injury related to glycemic and nonglycemic metabolic features of diabetes, and examines the effect of diabetic therapies. Data Sources and Study Selection A MEDLINE/PubMed search from inception to August 1, 2008, was conducted using the search terms acute lung injury, acute respiratory distress syndrome, hyperglycemia, diabetes mellitus, insulin, hydroxymethylglutaryl-CoA reductase inhibitors (statins), angiotensin-converting enzyme inhibitor, and peroxisome proliferator-activated receptors, including combinations of these terms. Bibliographies of retrieved articles were manually reviewed. Data Extraction and Synthesis Available studies were critically reviewed, and data were extracted with special attention to the human and animal studies that explored a) diabetes and ALI; b) hyperglycemia and ALI; c) metabolic nonhyperglycemic features of diabetes and ALI; and d) diabetic therapies and ALI. Conclusions Clinical and experimental data indicate that diabetes is protective against the development of ALI/ARDS. The pathways involved are complex and likely include effects of hyperglycemia on the inflammatory response, metabolic abnormalities in diabetes, and the interactions of therapeutic agents given to diabetic patients. Multidisciplinary, multifaceted studies, involving both animal models and clinical and molecular epidemiology techniques, are essential. PMID:19531947

Risk Prediction Models for Acute Kidney Injury in Critically Ill Patients: Opus in Progressu.

PubMed

Neyra, Javier A; Leaf, David E

2018-05-31

Acute kidney injury (AKI) is a complex systemic syndrome associated with high morbidity and mortality. Among critically ill patients admitted to intensive care units (ICUs), the incidence of AKI is as high as 50% and is associated with dismal outcomes. Thus, the development and validation of clinical risk prediction tools that accurately identify patients at high risk for AKI in the ICU is of paramount importance. We provide a comprehensive review of 3 clinical risk prediction tools that have been developed for incident AKI occurring in the first few hours or days following admission to the ICU. We found substantial heterogeneity among the clinical variables that were examined and included as significant predictors of AKI in the final models. The area under the receiver operating characteristic curves was ∼0.8 for all 3 models, indicating satisfactory model performance, though positive predictive values ranged from only 23 to 38%. Hence, further research is needed to develop more accurate and reproducible clinical risk prediction tools. Strategies for improved assessment of AKI susceptibility in the ICU include the incorporation of dynamic (time-varying) clinical parameters, as well as biomarker, functional, imaging, and genomic data. © 2018 S. Karger AG, Basel.

Bronchoscopy-Derived Correlates of Lung Injury Following Inhalational Injuries: A Prospective Obervational Study

EPA Science Inventory

Acute lung injury (ALI) is a major factor determining morbidity following burns and inhalational injury. In experimental models, factors potentially contributing to ALI risk include inhalation of toxins directly causing cell damage; inflammation; and infection. However, few studi...

ESTIMATING ACUTE AND CRONIC TOXICITY OF CHEMICALS FOR ENDANGERED FISHES

EPA Science Inventory

Predictive toxicological models, including estimates of uncertainty, are necessary to perform probability-based ecological risk assessments. This is particularly true for the protection of endangered species that are not prudent to test, other species that have not been tested o...

Allodynia Is Associated With Initial and Sustained Response to Acute Migraine Treatment: Results from the American Migraine Prevalence and Prevention Study.

PubMed

Lipton, Richard B; Munjal, Sagar; Buse, Dawn C; Bennett, Alix; Fanning, Kristina M; Burstein, Rami; Reed, Michael L

2017-07-01

In a population sample of persons with migraine treating with a single category of acute migraine medication, to identify rates and factors associated with acute treatment outcomes, including 2-hour pain freedom (2hPF), 24-hour pain response (24hPR), and 24-hour sustained pain response (24hSPR). Key predictors include acute treatment type (triptans and other medication categories), the influence of allodynia on response to medication, and the interaction between medication category and presence of allodynia in response to treatment among people with migraine. Cutaneous allodynia was previously associated with inadequate 2hPF, 24hPR, and 24hSPR (sustained response at 24 hours among those with adequate 2hPF) among people with migraine in the American Migraine Prevalence and Prevention (AMPP) Study. The AMPP Study obtained data from a representative US sample of persons with migraine by mailed questionnaire. The 2006 survey included 8233 people with migraine aged 18 or over who completed the Migraine Treatment Optimization Questionnaire (mTOQ). mTOQ was used to assess acute treatment outcomes including 2hPF, 24hPR, and 24hSPR. Eligible individuals used only a single category of acute prescription migraine treatments (n  =  5236, 63.6%). This sample was stratified into 5 categories of type of acute prescription headache medication used (triptans, nonsteroidal anti-inflammatory drugs, barbiturate-combinations, opioids, and opioid combinations and ergot alkaloids). Separate binary logistic regression models evaluated: (1) triptans vs other medication types; (2) presence of allodynia vs no allodynia; and (3) the interaction of medication category with allodynia. Sociodemographic variables, health insurance status, over-the-counter and preventive medication use were included as covariates. Odds ratios (OR) and 95% confidence intervals (CI) were generated for each acute treatment outcome. Among eligible participants, the mean age was 46 years, and 82.5% were women. The triptan use group had better outcomes than other medication groups for 2hPF (OR range: 2.00-2.63, all significant except ergot alkaloids) and 24hPR (OR range: 2.10-6.22, all significant). No significant medication effects were found for the 24hSPR outcome. The presence of allodynia was associated with significantly worse outcomes for both 2hPF (OR range: 1.42-1.55, all significant) and 24hPR (OR range: 1.30-1.32, all significant, except for ergot alkaloids, P  =  .051). Allodynia effects were not significant for the 24hSPR. The interaction between medication and allodynia was also not significant (OR range for 2hPF: .68-2.02; OR range for 2hPR: .35-1.34; OR range for 24hSPR: 1.21-2.72) in any of the models, suggesting allodynia is an important predictor of treatment response regardless of the medication group prescribed. The use of triptan medication was associated with significantly better 2hPF (except vs ergot alkaloids) and significantly better 24hPR outcomes compared with other acute medication categories. The presence of allodynia significantly increased the likelihood of an inadequate treatment response for both of these outcomes. Triptan use was generally associated with the best outcomes. Because allodynia was associated with inadequate outcomes for all medication groups, we suggest that allodynia is an area of unmet treatment need. © 2017 American Headache Society.

Functional status predicts acute care readmission in the traumatic spinal cord injury population.

PubMed

Huang, Donna; Slocum, Chloe; Silver, Julie K; Morgan, James W; Goldstein, Richard; Zafonte, Ross; Schneider, Jeffrey C

2018-03-29

Context/objective Acute care readmission has been identified as an important marker of healthcare quality. Most previous models assessing risk prediction of readmission incorporate variables for medical comorbidity. We hypothesized that functional status is a more robust predictor of readmission in the spinal cord injury population than medical comorbidities. Design Retrospective cross-sectional analysis. Setting Inpatient rehabilitation facilities, Uniform Data System for Medical Rehabilitation data from 2002 to 2012 Participants traumatic spinal cord injury patients. Outcome measures A logistic regression model for predicting acute care readmission based on demographic variables and functional status (Functional Model) was compared with models incorporating demographics, functional status, and medical comorbidities (Functional-Plus) or models including demographics and medical comorbidities (Demographic-Comorbidity). The primary outcomes were 3- and 30-day readmission, and the primary measure of model performance was the c-statistic. Results There were a total of 68,395 patients with 1,469 (2.15%) readmitted at 3 days and 7,081 (10.35%) readmitted at 30 days. The c-statistics for the Functional Model were 0.703 and 0.654 for 3 and 30 days. The Functional Model outperformed Demographic-Comorbidity models at 3 days (c-statistic difference: 0.066-0.096) and outperformed two of the three Demographic-Comorbidity models at 30 days (c-statistic difference: 0.029-0.056). The Functional-Plus models exhibited negligible improvements (0.002-0.010) in model performance compared to the Functional models. Conclusion Readmissions are used as a marker of hospital performance. Function-based readmission models in the spinal cord injury population outperform models incorporating medical comorbidities. Readmission risk models for this population would benefit from the inclusion of functional status.

Study of blood and brain lithium pharmacokinetics in the rat according to three different modalities of poisoning.

PubMed

Hanak, Anne-Sophie; Chevillard, Lucie; El Balkhi, Souleiman; Risède, Patricia; Peoc'h, Katell; Mégarbane, Bruno

2015-01-01

Lithium-induced neurotoxicity may be life threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg Li₂CO₃ in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg Li₂CO₃ in rats receiving 800 mg/l Li₂CO₃ in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg Li₂CO₃ during 5 days in rats with 15 mg/kg K₂Cr₂O₇-induced renal failure). Delayed absorption (4.03 vs 0.31 h), increased plasma elimination (0.65 vs 0.37 l/kg/h) and shorter half-life (1.75 vs 2.68 h) were observed in acute-on-chronically compared with acutely poisoned rats. Erythrocyte and cerebrospinal fluid kinetics paralleled plasma kinetics in both models. Brain lithium distribution was rapid (as early as 15 min), inhomogeneous and with delayed elimination (over 78 h). However, brain lithium accumulation was more marked in acute-on-chronically than acutely poisoned rats [area-under-the-curve of brain concentrations (379 ± 41 vs 295 ± 26, P < .05) and brain-to-plasma ratio (45 ± 10 vs 8 ± 2, P < .0001) at 54 h]. Moreover, brain lithium distribution was increased in chronically compared with acute-on-chronically poisoned rats (brain-to-plasma ratio: 9 ± 1 vs 3 ± 0, P < .01). In conclusion, prolonged rat exposure results in brain lithium accumulation, which is more marked in the presence of renal failure. Our data suggest that differences in plasma and brain kinetics may at least partially explain the observed variability between human intoxication patterns. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Assessment of recovery in older patients hospitalized with different diagnoses and functional levels, evaluated with and without geriatric assessment.

PubMed

Abrahamsen, Jenny Foss; Haugland, Cathrine; Ranhoff, Anette Hylen

2016-01-01

The objective of the present study was to investigate 1) the role of different admission diagnoses and 2) the degree of functional loss, on the rate of recovery of older patients after acute hospitalization. Furthermore, to compare the predictive value of simple assessments that can be carried out in a hospital lacking geriatric service, with assessments including geriatric screening tests. Prospective, observational cohort study, including 961community dwelling patients aged ≥ 70 years, transferred from medical, cardiac, pulmonary and orthopedic acute hospital departments to intermediate care in nursing home. Functional assessment with Barthel index (BI) was performed at admission to the nursing home and further geriatric assessment tests was performed during the first week. Logistic regression models with and without geriatric assessment were compared concerning the patients having 1) slow recovery (nursing home stay up to 2 months before return home) or, 2) poor recovery (dead or still in nursing home at 2 months). Slow recovery was independently associated with a diagnosis of non-vertebral fracture, BI subgroups 50-79 and <50, and, in the model including geriatric assessment, also with cognitive impairment. Poor recovery was more complex, and independently associated both with BI < 50, receiving home care before admission, higher age, admission with a non-vertebral fracture, and in the geriatric assessment model, cognitive impairment. Geriatric assessment is optimal for determining the recovery potential of older patients after acute hospitalization. As some hospitals lack geriatric services and ability to perform geriatric screening tests, a simpler assessment based on admission diagnoses and ADL function (BI), gives good information regarding the possible rehabilitation time and possibility to return home.

Development and validation of a risk-prediction nomogram for in-hospital mortality in adults poisoned with drugs and nonpharmaceutical agents

PubMed Central

Lionte, Catalina; Sorodoc, Victorita; Jaba, Elisabeta; Botezat, Alina

2017-01-01

Abstract Acute poisoning with drugs and nonpharmaceutical agents represents an important challenge in the emergency department (ED). The objective is to create and validate a risk-prediction nomogram for use in the ED to predict the risk of in-hospital mortality in adults from acute poisoning with drugs and nonpharmaceutical agents. This was a prospective cohort study involving adults with acute poisoning from drugs and nonpharmaceutical agents admitted to a tertiary referral center for toxicology between January and December 2015 (derivation cohort) and between January and June 2016 (validation cohort). We used a program to generate nomograms based on binary logistic regression predictive models. We included variables that had significant associations with death. Using regression coefficients, we calculated scores for each variable, and estimated the event probability. Model validation was performed using bootstrap to quantify our modeling strategy and using receiver operator characteristic (ROC) analysis. The nomogram was tested on a separate validation cohort using ROC analysis and goodness-of-fit tests. Data from 315 patients aged 18 to 91 years were analyzed (n = 180 in the derivation cohort; n = 135 in the validation cohort). In the final model, the following variables were significantly associated with mortality: age, laboratory test results (lactate, potassium, MB isoenzyme of creatine kinase), electrocardiogram parameters (QTc interval), and echocardiography findings (E wave velocity deceleration time). Sex was also included to use the same model for men and women. The resulting nomogram showed excellent survival/mortality discrimination (area under the curve [AUC] 0.976, 95% confidence interval [CI] 0.954–0.998, P < 0.0001 for the derivation cohort; AUC 0.957, 95% CI 0.892–1, P < 0.0001 for the validation cohort). This nomogram provides more precise, rapid, and simple risk-analysis information for individual patients acutely exposed to drugs and nonpharmaceutical agents, and accurately estimates the probability of in-hospital death, exclusively using the results of objective tests available in the ED. PMID:28328838

Sex differences in acute kidney injury requiring dialysis.

PubMed

Neugarten, Joel; Golestaneh, Ladan; Kolhe, Nitin V

2018-06-08

Female sex has been included as a risk factor in models developed to predict the risk of acute kidney injury (AKI) associated with cardiac surgery, aminoglycoside nephrotoxicity and contrast-induced nephropathy. The commentary acompanying the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury concludes that female sex is a shared susceptibility factor for acute kidney injury based on observations that female sex is associated with the development of hospital-acquired acute kidney injury. In contrast, female sex is reno-protective in animal models. In this context, we sought to examine the role of sex in hospital-associated acute kidney injury in greater detail. We utilized the Hospital Episode Statistics database to calculate the sex-stratified incidence of AKI requiring renal replacement therapy (AKI-D) among 194,157,726 hospital discharges reported for the years 1998-2013. In addition, we conducted a systematic review of the English literature to evaluate dialysis practices among men versus women with AKI. Hospitalized men were more likely to develop AKI-D than hospitalized women (OR 2.19 (2.15, 2.22) p < 0.0001). We found no evidence in the published literature that dialysis practices differ between men and women with AKI. Based on a population of hospitalized patients which is more than 3 times larger than all previously published cohorts reporting sex-stratified AKI data combined, we conclude that male sex is associated with an increased incidence of hospital-associated AKI-D. Our study is among the first reports to highlight the protective role of female gender in AKI.

Fisetin administration improves LPS-induced acute otitis media in mouse in vivo.

PubMed

Li, Peng; Chen, Dan; Huang, Yang

2018-07-01

Acute otitis media is one of the most common infectious diseases worldwide in spite of the widespread vaccination. The present study was conducted to explore the effects of fisetin on mouse acute otitis media models. The animal models were established by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Fisetin was administered to mice for ten days through intragastric administration immediate after LPS application. Hematoxylin and eosin (H&E) staining was performed and the pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 and VEGF, were measured through enzyme-linked immunosorbent assay (ELISA) method and RT-qPCR analysis. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was detected by immunoblotting assays. Reactive oxygen species (ROS) generated levels were determined through assessment of anti-oxidants, and TXNIP/MAPKs signaling pathways were explored to reveal the possible molecular mechanism for acute otitis media progression and the function of fisetin. Fisetin reduced mucosal thickness caused by LPS. In fisetin-treated animals, pro-inflammatory cytokine release was downregulated accompanied with TLR4/NF-κB inactivation. ROS production was significantly decreased in comparison to the LPS-treated group. The TXNIP/MAPKs signaling pathway was inactivated for fisetin treatment in LPS-induced mice with acute otitis media. The above results indicated that fisetin improved acute otitis media through inflammation and ROS suppression via inactivating TLR4/NF-κB and TXNIP/MAPKs signaling pathways.

Fisetin administration improves LPS-induced acute otitis media in mouse in vivo

PubMed Central

Li, Peng; Chen, Dan; Huang, Yang

2018-01-01

Acute otitis media is one of the most common infectious diseases worldwide in spite of the widespread vaccination. The present study was conducted to explore the effects of fisetin on mouse acute otitis media models. The animal models were established by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Fisetin was administered to mice for ten days through intragastric administration immediate after LPS application. Hematoxylin and eosin (H&E) staining was performed and the pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 and VEGF, were measured through enzyme-linked immunosorbent assay (ELISA) method and RT-qPCR analysis. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was detected by immunoblotting assays. Reactive oxygen species (ROS) generated levels were determined through assessment of anti-oxidants, and TXNIP/MAPKs signaling pathways were explored to reveal the possible molecular mechanism for acute otitis media progression and the function of fisetin. Fisetin reduced mucosal thickness caused by LPS. In fisetin-treated animals, pro-inflammatory cytokine release was downregulated accompanied with TLR4/NF-κB inactivation. ROS production was significantly decreased in comparison to the LPS-treated group. The TXNIP/MAPKs signaling pathway was inactivated for fisetin treatment in LPS-induced mice with acute otitis media. The above results indicated that fisetin improved acute otitis media through inflammation and ROS suppression via inactivating TLR4/NF-κB and TXNIP/MAPKs signaling pathways. PMID:29568876

Carbon monoxide-bound hemoglobin vesicles ameliorate multiorgan injuries induced by severe acute pancreatitis in mice by their anti-inflammatory and antioxidant properties.

PubMed

Nagao, Saori; Taguchi, Kazuaki; Sakai, Hiromi; Yamasaki, Keishi; Watanabe, Hiroshi; Otagiri, Masaki; Maruyama, Toru

Carbon monoxide (CO) has attracted attention as a possible therapeutic agent for affecting anti-inflammatory and antioxidant activities. Previously, CO-bound hemoglobin vesicle (CO-HbV) was developed as a nanotechnology-based CO donor, and its safety profile and therapeutic potential as a clinically applicable carrier of CO were examined in vitro and in vivo. In the present study, the therapeutic efficacy of CO-HbV against severe acute pancreatitis was examined with secondary distal organ-injured model mice that were fed with a choline-deficient ethionine-supplemented diet. A CO-HbV treatment significantly reduced the mortality of the acute pancreatitis model mice compared to saline and HbV. Biochemical and histological evaluations clearly showed that CO-HbV suppressed acute pancreatitis by inhibiting the production of systemic proinflammatory cytokines, neutrophil infiltration, and oxidative injuries in pancreatic tissue. Interestingly, CO-HbV also diminished the subsequent damage to distal organs including liver, kidneys, and lungs. This could be due to the suppression of neutrophil infiltration into tissues and the subsequently enhanced oxidative injuries. In contrast, O 2 -bound HbV, the inactive form of CO-HbV, was ineffective against both pancreatitis and distal organ injuries, confirming that CO was directly responsible for the protective effects of CO-HbV in acute pancreatitis. These findings suggest that CO-HbV has anti-inflammatory and antioxidant characteristics of CO and consequently exerts a superior protective effect against acute pancreatitis-induced multiorgan damage.

Revalidation of the Score for Neonatal Acute Physiology in the Vermont Oxford Network.

PubMed

Zupancic, John A F; Richardson, Douglas K; Horbar, Jeffrey D; Carpenter, Joseph H; Lee, Shoo K; Escobar, Gabriel J

2007-01-01

Our specific objectives were (1) to document the performance of the revised Score for Neonatal Acute Physiology and the revised Score for Neonatal Acute Physiology Perinatal Extension in predicting death in the Vermont Oxford Network, compared with published normative values; (2) to determine whether this performance could be improved through recalibration of the weights for individual score items; (3) to determine the impact of including congenital anomalies in the predictive model; and (4) to compare performance against that of the Vermont Oxford Network risk adjustment, separately and in combination. Fifty-eight Vermont Oxford Network centers collected data prospectively for the revised Score for Neonatal Acute Physiology in the first 12 hours after admission of infants in 2002. Data were collected for 10,469 infants, and analyses were undertaken for 9897 who met inclusion criteria. The median revised Score for Neonatal Acute Physiology was 5, and the mean birth weight was 1951 g. Recalibration of the revised Score for Neonatal Acute Physiology and revised Score for Neonatal Acute Physiology Perinatal Extension resulted in minimal changes in their discriminatory abilities. The Vermont Oxford Network risk adjustment performed similarly, compared with the revised Score for Neonatal Acute Physiology Perinatal Extension. Current score performance was similar to that observed previously, which suggests that the revised Score for Neonatal Acute Physiology and revised Score for Neonatal Acute Physiology Perinatal Extension have not decalibrated over the 7 years since the first cohort was assembled, despite advances in neonatal care during that period. Addition of congenital anomalies to the revised Score for Neonatal Acute Physiology Perinatal Extension improved discrimination significantly, particularly for infants with birth weights of >1500 g. The Vermont Oxford Network risk adjustment performed similarly, compared with the revised Score for Neonatal Acute Physiology Perinatal Extension.

The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism

PubMed Central

Sonsalla, Patricia K.; Coleman, Christal; Wong, Lai-Yoong; Harris, Suzan L.; Richardson, Jason R.; Gadad, Bharathi S.; Li, Wenhao; German, Dwight C.

2013-01-01

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by a prominent loss of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. The peptide angiotensin II (AngII) plays a role in oxidative-stress induced disorders and is thought to mediate its detrimental actions via activation of AngII AT1 receptors. The brain renin-angiotensin system is implicated in neurodegenerative disorders including PD. Blockade of the angiotensin converting enzyme or AT1 receptors provides protection in acute animal models of parkinsonism. We demonstrate here that treatment of mice with the angiotensin converting enzyme inhibitor captopril protects the striatum from acutely administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP), and that chronic captopril protects the nigral DA cell bodies from degeneration in a progressive rat model of parkinsonism created by the chronic intracerebral infusion of 1-methyl-4-phenylpyridinium (MPP+). The accompanying activation of microglia in the substantia nigra of MPP+-treated rats was reduced by the chronic captopril treatment. These findings indicate that captopril is neuroprotective for nigrostriatal DA neurons in both acute and chronic rodent PD models. Targeting the brain AngII pathway may be a feasible approach to slowing neurodegeneration in PD. PMID:24184050

Accuracy of dengue clinical diagnosis with and without NS1 antigen rapid test: Comparison between human and Bayesian network model decision.

PubMed

Sa-Ngamuang, Chaitawat; Haddawy, Peter; Luvira, Viravarn; Piyaphanee, Watcharapong; Iamsirithaworn, Sopon; Lawpoolsri, Saranath

2018-06-18

Differentiating dengue patients from other acute febrile illness patients is a great challenge among physicians. Several dengue diagnosis methods are recommended by WHO. The application of specific laboratory tests is still limited due to high cost, lack of equipment, and uncertain validity. Therefore, clinical diagnosis remains a common practice especially in resource limited settings. Bayesian networks have been shown to be a useful tool for diagnostic decision support. This study aimed to construct Bayesian network models using basic demographic, clinical, and laboratory profiles of acute febrile illness patients to diagnose dengue. Data of 397 acute undifferentiated febrile illness patients who visited the fever clinic of the Bangkok Hospital for Tropical Diseases, Thailand, were used for model construction and validation. The two best final models were selected: one with and one without NS1 rapid test result. The diagnostic accuracy of the models was compared with that of physicians on the same set of patients. The Bayesian network models provided good diagnostic accuracy of dengue infection, with ROC AUC of 0.80 and 0.75 for models with and without NS1 rapid test result, respectively. The models had approximately 80% specificity and 70% sensitivity, similar to the diagnostic accuracy of the hospital's fellows in infectious disease. Including information on NS1 rapid test improved the specificity, but reduced the sensitivity, both in model and physician diagnoses. The Bayesian network model developed in this study could be useful to assist physicians in diagnosing dengue, particularly in regions where experienced physicians and laboratory confirmation tests are limited.

Acute radiation enteritis caused by dose-dependent radiation exposure in dogs: experimental research.

PubMed

Xu, Wenda; Chen, Jiang; Xu, Liu; Li, Hongyu; Guo, Xiaozhong

2014-12-01

Accidental or intended radiation exposure in mass casualty settings presents a serious and on-going threat. The development of mitigating and treating agents requires appropriate animal models. Unfortunately, the majority of research on radiation enteritis in animals has lacked specific assessments and targeted therapy. Our study showed beagle dogs, treated by intensity-modulated radiation therapy (IMRT) for abdominal irradiation, were administered single X-ray doses of 8-30 Gy. The degree of intestinal tract injury for all of the animals after radiation exposure was evaluated with regard to clinical syndrome, endoscopic findings, histological features, and intestinal function. The range of single doses (8 Gy, 10-14 Gy, and 16-30 Gy) represented the degree of injury (mild, moderate, and severe, respectively). Acute radiation enteritis included clinical syndrome with fever, vomiting, diarrhea, hemafecia, and weight loss; typical endoscopic findings included edema, bleeding, mucosal abrasions, and ulcers; and intestinal biopsy results revealed mucosal necrosis, erosion, and loss, inflammatory cell infiltration, hemorrhage, and congestion. Changes in serum diamine oxides (DAOs) and d-xylose represented intestinal barrier function and absorption function, respectively, and correlated with the extent of damage (P < 0.05 and P < 0.05, respectively). We successfully developed a dog model of acute radiation enteritis, thus obtaining a relatively objective evaluation of intestinal tract injury based on clinical performance and laboratory examination. The method of assessment of the degree of intestinal tract injury after abdominal irradiation could be beneficial in the development of novel and effective therapeutic strategies for acute radiation enteritis. © 2014 by the Society for Experimental Biology and Medicine.

Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury.

PubMed

Ritter, Anne C; Wagner, Amy K; Szaflarski, Jerzy P; Brooks, Maria M; Zafonte, Ross D; Pugh, Mary Jo V; Fabio, Anthony; Hammond, Flora M; Dreer, Laura E; Bushnik, Tamara; Walker, William C; Brown, Allen W; Johnson-Greene, Doug; Shea, Timothy; Krellman, Jason W; Rosenthal, Joseph A

2016-09-01

Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury. Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011-2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value < 0.20 that were used to fit initial prognostic models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism). The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively. The prognostic model for PTS during acute hospitalization did not discriminate well. Year 1 and year 2 models showed fair to good predictive validity for PTS. Cranial surgery, although medically necessary, requires ongoing research regarding potential benefits of increased monitoring for signs of epileptogenesis, PTS prophylaxis, and/or rehabilitation/social support. Future studies should externally validate models and determine clinical utility. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

DTIC Science & Technology

2016-07-01

removal of excess glutamate from the brain. Scope: We will test this novel and powerful neuroprotective treatment in a rat model of repetitive mild...neuroprotective treatment in a rat model of a single moderate TBI and in a rat model of repetitive mild (concussive) TBIs. Outcome measures include...Troubleshooting and refinement of CSF extraction resulting in reliable measurement of glutamate in CSF. 5 Effects of treatment on rotarod motor deficits

Acute-On-Chronic Liver Failure: Causes, Clinical Characteristics and Predictors of Mortality.

PubMed

Tasneem, Abbas Ali; Luck, Nasir Hassan

2017-01-01

To determine the causes, characteristics and predictors of mortality in patients with acute-on-chronic liver failure (ACLF). Cross-sectional study. Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi, from July 2014 to June 2016. All patients with acute-on-chronic liver disease (ACLD) with ages > 12 were included. Patients with ACLF, as defined by the Asian Pacific Association for the Study of Liver (APASL, 2014) were identified. Predictors of mortality were identified using chi-square or Fisher's exact test. Included in the study were 72 patients with mean age of 36.71 years, 46 (63.9%) being males. Among them, 61 developed ACLF. Commonest causes of chronic liver disease (CLD) were chronic viral hepatitis (37, 51.4%) and autoimmune hepatitis (14, 19.4%). Commonest causes of acute liver injury (ALI) were acute viral hepatitis (24, 33.3%) and drug induced liver injury (DILI) (17, 23.6%). Among those with ACLF, 24 (39.3%) patients died with median survival of 17.1 ±13.5 days. Mortality was significantly associated with Child Turcotte Pugh (CTP) score ≥13 (p=0.010), model for end-stage liver disease (MELD) score ≥30 (p=0.001), age >40 years (p=0.036), organ failures (OF) ≥3 (p <0.0001), portosystemic encephalopathy (PSE) (p <0.0001), renal failure (p <0.0001) and urosepsis (p <0.0001). Acute viral hepatitis and DILI are commonest causes of ACLF. Mortality is high in ACLF patients having OF ≥3, CTP ≥13, MELD ≥30, age >40 years, PSE, renal failure and urosepsis.

Cost-effectiveness analysis of personalized antiplatelet therapy in patients with acute coronary syndrome.

PubMed

Jiang, Minghuan; You, Joyce Hs

2016-05-01

This study aimed to compare the clinical and economic outcomes of pharmacogenetic-guided (PG-guided) and platelet reactivity testing-guided antiplatelet therapy for patients with acute coronary syndrome undergoing percutaneous coronary intervention. A decision-analytic model was simulated including four antiplatelet strategies: universal clopidogrel 75 mg daily, universal alternative P2Y12 inhibitor (prasugrel or ticagrelor), PG-guided therapy, and platelet reactivity testing-guided therapy. PG-guided therapy was the preferred option with lowest cost (US$75,208) and highest quality-adjusted life years gained (7.6249 quality-adjusted life years). The base-case results were robust in sensitivity analysis. PG-guided antiplatelet therapy showed the highest probability to be preferred antiplatelet strategy for acute coronary syndrome patients with percutaneous coronary intervention.

Monocytic leukemias.

PubMed

Shaw, M T

1980-05-01

The monocytic leukemias may be subdivided into acute monocytic leukemia, acute myelomonocytic leukemia, and subacute and chronic myelomonocytic leukemia. The clinical features of acute monocytic and acute myelomonocytic leukemias are similar and are manifestations of bone marrow failure. Gingival hypertrophy and skin infiltration are more frequent in acute monocytic leukemia. Cytomorphologically the blast cells in acute monocytic leukemia may be undifferentiated or differentiated, whereas in the acute myelomonocytic variety there are mixed populations of monocytic and myeloblastic cells. Cytochemical characteristics include strongly positive reactions for nonspecific esterase, inhibited by fluoride. The functional characteristics of acute monocytic and acute myelomonocytic cells resemble those of monocytes and include glass adherence and phagocytoses, the presence of Fc receptors for IgG and C'3, and the production of colony stimulating activity. Subacute and chronic myelomonocytic leukemias are insidious and slowly progressive diseases characterized by anemia and peripheral blood monocytosis. Atypical monocytes called paramyeloid cells are characteristic. The drugs used in the treatment of acute monocytic and acute myelomonocytic leukemias include cytosine arabinoside, the anthracyclines, and VP 16-213. Drug therapy in subacute and chronic myelomonocytic leukemias is not usually indicated, although VP 16-213 has been claimed to be effective.

The first dedicated life sciences mission - Spacelab 4

NASA Technical Reports Server (NTRS)

Cramer, D. R.; Reid, D. H.; Klein, H. P.

1983-01-01

The details of the payload and the experiments in Spacelab 4, the first Spacelab mission dedicated entirely to the life sciences, are discussed. The payload of Spacelab 4, carried in the bay of the Shuttle Orbiter, consists of 25 tentatively selected investigations combined into a comprehensive integrated exploration of the effects of acute weightlessness on living systems. The payload contains complementary designs in the human and animal investigations in order to validate animal models of human physiology in weightlessness. Animals used as experimental subjects will include squirrel monkeys, laboratory rats, several species of plants, and frog eggs. The main scientific objectives of the investigations include the study of the acute cephalic fluid shift, cardiovascular adaptation to weightlessness, including postflight reductions in orthostatic tolerance and exercise capacity, and changes in vestibular function, including space motion sickness, associated with weightlessness. Other scientific objective include the study of red cell mass reduction, negative nitrogen balance, altered calcium metabolism, suppressed in vitro lymphocyte reactivity, gravitropism and photropism in plants, and fertilization and early development in frog eggs.

QSAR Modeling of Rat Acute Toxicity by Oral Exposure

PubMed Central

Zhu, Hao; Martin, Todd M.; Ye, Lin; Sedykh, Alexander; Young, Douglas M.; Tropsha, Alexander

2009-01-01

Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. In this study, a comprehensive dataset of 7,385 compounds with their most conservative lethal dose (LD50) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire dataset was selected that included all 3,472 compounds used in the TOPKAT’s training set. The remaining 3,913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R2 of linear regression between actual and predicted LD50 values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R2 ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD50 for every compound using all 5 models. The consensus models afforded higher prediction accuracy for the external validation dataset with the higher coverage as compared to individual constituent models. The validated consensus LD50 models developed in this study can be used as reliable computational predictors of in vivo acute toxicity. PMID:19845371

Quantitative structure-activity relationship modeling of rat acute toxicity by oral exposure.

PubMed

Zhu, Hao; Martin, Todd M; Ye, Lin; Sedykh, Alexander; Young, Douglas M; Tropsha, Alexander

2009-12-01

Few quantitative structure-activity relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity end points. In this study, a comprehensive data set of 7385 compounds with their most conservative lethal dose (LD(50)) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire data set was selected that included all 3472 compounds used in TOPKAT's training set. The remaining 3913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R(2) of linear regression between actual and predicted LD(50) values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R(2) ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD(50) for every compound using all five models. The consensus models afforded higher prediction accuracy for the external validation data set with the higher coverage as compared to individual constituent models. The validated consensus LD(50) models developed in this study can be used as reliable computational predictors of in vivo acute toxicity.

Expression and clinical significance of rhubarb on serum amylase and TNF-alpha of rat model of acute pancreatitis.

PubMed

Zhang, W F; Li, Z T; Fang, J J; Wang, G B; Yu, Y; Liu, Z Q; Wu, Y N; Zheng, S S; Cai, L

2017-01-01

The aim of this study was to evaluate the therapeutic effect of rhubarb extract on acute pancreatitis. Ninety-six healthy Sprague Dawley rats, weighing 301±5.12 g were randomly divided into 4 groups: sham surgery (group A), acute pancreatitis model (group B), acute pancreatitis with normal saline (group C), and acute pancreatitis model with rhubarb (group D). The levels of serum amylase (AMY) and TNF-α were measured at 1st, 6th, 12th and 24th hour after modeling, and the pancreatic tissue were used to observe the pathologic changes. Compared to the sham group, the serum AMY and serum tumor necrosis factor (TNF-α) levels were significantly increased in the other groups (p <0.05). Compared to the model group and the saline group, the serum AMY, serum TNF-α level and pathological changes of rats in the rhubarb group were significantly lower (p <0.05). The serum AMY and TNF-α levels increased in acute pancreatitis. The rhubarb reduced the serum AMY and TNF-α level in rats with acute pancreatitis and reduced the pathological changes of pancreas and other tissues.

The Peripheral Whole Blood Transcriptome of Acute Pyelonephritis in Human Pregnancy

PubMed Central

Madan, Ichchha; Than, Nandor Gabor; Romero, Roberto; Chaemsaithong, Piya; Miranda, Jezid; Tarca, Adi L.; Bhatti, Gaurav; Draghici, Sorin; Yeo, Lami; Mazor, Moshe; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn

2018-01-01

Objective Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection to the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis. Method A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analysis were applied. Results A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were up-regulated and 526 were down-regulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included a) cytokine-cytokine receptor interaction; b) T-cell receptor signaling; c) Jak-STAT signaling; and d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression. Conclusion This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is associated with the increased expression of genes involved in innate immunity and the decreased expression of genes involved in lymphocyte function. PMID:24293448

A transitional care service for elderly chronic disease patients at risk of readmission.

PubMed

Brand, Caroline A; Jones, Catherine T; Lowe, Adrian J; Nielsen, David A; Roberts, Carol A; King, Bellinda L; Campbell, Donald A

2004-12-13

Multiple hospital admissions, especially those related to chronic disease, represent a particular challenge to the acute health care sector in Australia. To determine whether a nurse-led chronic disease management model of transitional care reduced readmissions to acute care. A quasi-experimental controlled trial. A large tertiary metropolitan teaching hospital. 166 general medical patients aged > or = 65 years with either a history of readmissions to acute care or multiple medical comorbidities. Implementation of a chronic disease management model of transitional care aimed at improving patient management and reducing readmissions to acute care. Readmission rates and emergency department presentation rates at 3-and 6-month follow up. Secondary outcome measures include quality of life, discharge destination, and primary health care service utilisation. There was no difference in readmission rates, emergency department presentation rates, quality of life, discharge destination or primary health care service utilisation. The difficulties inherent in evaluating this type of multifactorial intervention are discussed and consideration is given to patient factors, the difficulty of influencing readmission rates, and local system issues. The outcomes of this study reflect the tension that exists between implementing multifaceted integrated health service programs and attempting to evaluate them within complex and changing environments using robust research methodologies.

Directional diffusivity as a magnetic resonance (MR) biomarker in demyelinating disease

NASA Astrophysics Data System (ADS)

Benzinger, Tammie L. S.; Cross, Anne H.; Xu, Junqian; Naismith, Robert; Sun, Shu-Wei; Song, Sheng-Kwei

2007-09-01

Directional diffusivities derived from diffusion tensor magnetic resonance imaging (DTI) measurements describe water movement parallel to (λ ||, axial diffusivity) and perpendicular to (λ⊥radial diffusivity) axonal tracts. λ || and λ⊥ have been shown to differentially detect axon and myelin abnormalities in several mouse models of central nervous system white matter pathology in our laboratory. These models include experimental autoimmune encephalomyelitis (EAE), (1) myelin basic protein mutant mice with dysmyelination and intact axons, (2) cuprizone-induced demyelination, and remyelination, with reversible axon injury (2, 3) and a model of retinal ischemia in which retinal ganglion cell death is followed by Wallerian degeneration of optic nerve, with axonal injury preceding demyelination. (4) Decreased λ|| correlates with acute axonal injury and increased λ⊥ indicates myelin damage. (4) More recently, we have translated this approach to human MR, investigating acute and chronic optic neuritis in adults with multiple sclerosis, brain lesions in adults with multiple sclerosis, and acute disseminated encephalomyelitis (ADEM) in children. We are also investigating the use of this technique to probe the underlying structural change of the cervical spinal cord in acute and chronic T2- hyperintense lesions in spinal stenosis, trauma, and transverse myelitis. In each of these demyelinating diseases, the discrimination between axonal and myelin injury which we can achieve has important prognostic and therapeutic implications. For those patients with myelin injury but intact axons, early, directed drug therapy has the potential to prevent progression to axonal loss and permanent disability.

Adoptive immunotherapy for B-cell malignancies using CD19-targeted chimeric antigen receptor T-cells: A systematic review of efficacy and safety.

PubMed

Hao, Lu; Li, Tongtong; Chang, Lung-Ji; Chen, Xiaochuan

2017-08-01

Adoptive infusion of chimeric antigen receptor transduced T-cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results. In this report, we performed a meta-analysis to evaluate the efficacy and side effects of CAR-T on relapsed B-cell malignancies, including leukemia and lymphoma. Clinical studies investigating efficacy and safety of CAR-T in acute and chronic lymphocytic leukemia and lymphoma were identified by searching PubMed and EMBASE. Outcomes of efficacy subjected to analysis were the rates of complete remission (CR) and partial remission (PR). The safety parameters were the prevalence of adverse effects including fever, hypotension, and acute renal failure. Meta analyses were performed using R software. Weighted hazard ratio (HR) with 95% confidence intervals was calculated for each outcome. Fixed or random-effects models were employed depending on the heterogeneity across the included studies. Nineteen published clinical studies, with a total of 391 patients were included for the meta-analysis. The pooled rate of complete remission was 55% (95% CI 41%-69%); the pooled rate of partial remission was 25% (95% CI: 19%-33%). The prevalence of fever was 62% (95% CI: 41%-79%); the hypotension was 22% (95% CI: 15%-31%); acute renal failure was 24% (95% CI: 16%-34%). All adverse effects were manageable and no death was reported due to toxicity. CD19-targeted CAR-T is an effective modality in treating refractory B-cell malignancies including acute and chronic lymphatic leukemia, Hodjkin's and non-Hodjkin's lymphoma. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Natural Models for Autonomous Control of Spatial Navigation, Sensing, and Guidance, Part 1

DTIC Science & Technology

2011-06-16

polarization sensitivity ten times more acute than previously documented in cephalopods (cuttlefish and octopus ) and crustaceans (mantis shrimps and crabs...responded to perceived looming stimuli in a number of ways, including swimming movements , skin colour and texture changes, which were recorded using

Predicting risk for portal vein thrombosis in acute pancreatitis patients: A comparison of radical basis function artificial neural network and logistic regression models.

PubMed

Fei, Yang; Hu, Jian; Gao, Kun; Tu, Jianfeng; Li, Wei-Qin; Wang, Wei

2017-06-01

To construct a radical basis function (RBF) artificial neural networks (ANNs) model to predict the incidence of acute pancreatitis (AP)-induced portal vein thrombosis. The analysis included 353 patients with AP who had admitted between January 2011 and December 2015. RBF ANNs model and logistic regression model were constructed based on eleven factors relevant to AP respectively. Statistical indexes were used to evaluate the value of the prediction in two models. The predict sensitivity, specificity, positive predictive value, negative predictive value and accuracy by RBF ANNs model for PVT were 73.3%, 91.4%, 68.8%, 93.0% and 87.7%, respectively. There were significant differences between the RBF ANNs and logistic regression models in these parameters (P<0.05). In addition, a comparison of the area under receiver operating characteristic curves of the two models showed a statistically significant difference (P<0.05). The RBF ANNs model is more likely to predict the occurrence of PVT induced by AP than logistic regression model. D-dimer, AMY, Hct and PT were important prediction factors of approval for AP-induced PVT. Copyright © 2017 Elsevier Inc. All rights reserved.

NMR-based metabonomic and quantitative real-time PCR in the profiling of metabolic changes in carbon tetrachloride-induced rat liver injury.

PubMed

Li, Xiaowei; Zhang, Fusheng; Wang, Dongqin; Li, Zhenyu; Qin, Xuemei; Du, Guanhua

2014-02-01

Carbon tetrachloride (CCl4) is commonly used as a model toxicant to induce chronic and acute liver injuries. In this study, metabolite profiling and gene expression analysis of liver tissues were performed by nuclear magnetic resonance and quantitative real-time polymerase chain reaction to understand the responses of acute liver injury system in rats to CCl4. Acute liver injury was successfully induced by CCl4 as revealed by histopathological results and significant increase in alanine aminotransferase and serum aspartate aminotransferase. We found that CCl4 caused a significant increase in lactate, succinate, citrate, dimethylgycine, choline and taurine. CCl4 also caused a decrease in some of the amino acids such as leucine/isoleucine, glutamine/glutathione and betaine. Gene function analysis revealed that 10 relevant enzyme genes exhibited changes in expressions in the acute liver injury model. In conclusion, the metabolic pathways, including tricarboxylic acid cycle, antioxidant defense systems, fatty acid β-oxidation, glycolysis and choline and mevalonate metabolisms were impaired in CCl4-treated rat livers. These findings provided an overview of the biochemical consequences of CCl4 exposure and comprehensive insights into the metabolic aspects of CCl4-induced hepatotoxicity in rats. These findings may also provide reference of the mechanisms of acute liver injury that could be used to study the changes in functional genes and metabolites. Copyright © 2013 Elsevier B.V. All rights reserved.

Acute risk factors for suicide attempts and death: prospective findings from the STEP-BD study

PubMed Central

Ballard, Elizabeth D; Vande Voort, Jennifer L; Luckenbaugh, David A; Machado-Vieira, Rodrigo; Tohen, Mauricio; Zarate, Carlos A

2016-01-01

Objectives Suicide is unfortunately common in psychiatric practice, but difficult to predict. This study sought to assess which clinical symptoms increase in the months before suicidal behavior in a sample of psychiatric outpatients with bipolar disorder. Methods Data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) trial were used. A total pf 103 participants who attempted suicide or died by suicide during the trial were included; a 15% random sample of the remaining participants (n = 427) was used as a comparison sample. Linear mixed models in the six months before suicidal behavior were conducted for each of five proposed acute risk factors for suicidal behavior. Participants were assessed using the Clinical Monitoring Form (CMF) at each visit for the following potential acute risk factors for suicidal behavior: suicidal ideation, loss of interest, anxiety, psychomotor agitation, and high-risk behavior. Results Each of the five symptoms was elevated overall in individuals who engaged in suicidal behavior (p < 0.05). The severity of both suicidal ideation and loss of interest significantly increased in the months before suicidal behavior (p < 0.001). Anxiety demonstrated comparable effect sizes across multiple models. Psychomotor agitation and high-risk behavior were not significantly elevated before suicidal behavior. Conclusions Suicidal ideation, loss of interest and, to a lesser extent, anxiety may represent acute suicide risk factors up to four months before suicidal behavior in outpatients with bipolar disorder. Further investigation of these potential acute risk factors in prospective analyses is warranted. PMID:27233466

Cytokines and T-Lymphocute count in patients in the acute and chronic phases of Bartonella bacilliformis infection in an endemic area in peru: a pilot study.

PubMed

Huarcaya, Erick; Best, Ivan; Rodriguez-Tafur, Juan; Maguiña, Ciro; Solórzano, Nelson; Menacho, Julio; Lopez De Guimaraes, Douglas; Chauca, Jose; Ventosilla, Palmira

2011-01-01

Human Bartonellosis has an acute phase characterized by fever and hemolytic anemia, and a chronic phase with bacillary angiomatosis-like lesions. This cross-sectional pilot study evaluated the immunology patterns using pre- and post-treatment samples in patients with Human Bartonellosis. Patients between five and 60 years of age, from endemic areas in Peru, in the acute or chronic phases were included. In patients in the acute phase of Bartonellosis a state of immune peripheral tolerance should be established for persistence of the infection. Our findings were that elevation of the anti-inflammatory cytokine IL-10 and numeric abnormalities of CD4(+) and CD8(+) T-Lymphocyte counts correlated significantly with an unfavorable immune state. During the chronic phase, the elevated levels of IFN-γ and IL-4 observed in our series correlated with previous findings of endothelial invasion of B. henselae in animal models.

Casemix and rehabilitation: evaluation of an early discharge scheme.

PubMed

Brandis, S

2000-01-01

This paper presents a case study of an early discharge scheme funded by casemix incentives and discusses limitations of a casemix model of funding whereby hospital inpatient care is funded separately from care in other settings. The POSITIVE Rehabilitation program received 151 patients discharged early from hospital in a twelve-month period. Program evaluation demonstrates a 40.9% drop in the average length of stay of rehabilitation patients and a 42.6% drop in average length of stay for patients with stroke. Other benefits of the program include a high level of patient satisfaction, improved carer support and increased continuity of care. The challenge under the Australian interpretation of a casemix model of funding is ensuring the viability of services that extend across acute hospital, non-acute care, and community and home settings.

In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury.

PubMed

Patsalos, Andreas; Pap, Attila; Varga, Tamas; Trencsenyi, Gyorgy; Contreras, Gerardo Alvarado; Garai, Ildiko; Papp, Zoltan; Dezso, Balazs; Pintye, Eva; Nagy, Laszlo

2017-09-01

The in situ phenotypic switch of macrophages is delayed in acute injury following irradiation. The combination of bone marrow transplantation and local muscle radiation protection allows for the identification of a myeloid cell contribution to tissue repair. PET-MRI allows monitoring of myeloid cell invasion and metabolism. Altered cellular composition prior to acute sterile injury affects the in situ phenotypic transition of invading myeloid cells to repair macrophages. There is reciprocal intercellular communication between local muscle cell compartments, such as PAX7 positive cells, and recruited macrophages during skeletal muscle regeneration. Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for clearance of necrotic debris and for coordination of tissue regeneration. This highly dynamic process is characterized by an in situ transition of infiltrating monocytes from an inflammatory (Ly6C high ) to a repair (Ly6C low ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology. Here, using an acute sterile skeletal muscle injury model combined with irradiation, bone marrow transplantation and in vivo imaging, we show that preserved muscle integrity and cell composition prior to the injury is necessary for the repair macrophage phenotypic transition and subsequently for proper and complete tissue regeneration. Importantly, by using a model of in vivo ablation of PAX7 positive cells, we show that this radiosensitive skeletal muscle progenitor pool contributes to macrophage phenotypic transition following acute sterile muscle injury. In addition, local muscle tissue radioprotection by lead shielding during irradiation preserves normal macrophage transition dynamics and subsequently muscle tissue regeneration. Taken together, our data suggest the existence of a more extensive and reciprocal cross-talk between muscle tissue compartments, including satellite cells, and infiltrating myeloid cells upon tissue damage. These interactions shape the macrophage in situ phenotypic shift, which is indispensable for normal muscle tissue repair dynamics. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

PubMed

Al-Absi, Boshra; Noor, Suzita M; Saif-Ali, Riyadh; Salem, Sameer D; Ahmed, Radwan H; Razif, Muhammad Fm; Muniandy, Sekaran

2017-04-01

Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was associated with protection against acute lymphoblastic leukemia. In conclusion, our study has shown that ARID5B variants are associated with acute lymphoblastic leukemia in Yemeni children with several gender biases of ARID5B single nucleotide polymorphisms reported.

Lipopolysaccharide-induced endotoxemia in corn oil-preloaded mice causes an extended course of lung injury and repair and pulmonary fibrosis: A translational mouse model of acute respiratory distress syndrome.

PubMed

Wu, Chaomin; Evans, Colin E; Dai, Zhiyu; Huang, Xiaojia; Zhang, Xianming; Jin, Hua; Hu, Guochang; Song, Yuanlin; Zhao, You-Yang

2017-01-01

Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure, bilateral pulmonary infiltrates, and pulmonary edema of non-cardiac origin. Effective treatments for ARDS patients may arise from experimental studies with translational mouse models of this disease that aim to delineate the mechanisms underlying the disease pathogenesis. Mouse models of ARDS, however, can be limited by their rapid progression from injured to recovery state, which is in contrast to the course of ARDS in humans. Furthermore, current mouse models of ARDS do not recapitulate certain prominent aspects of the pathogenesis of ARDS in humans. In this study, we developed an improved endotoxemic mouse model of ARDS resembling many features of clinical ARDS including extended courses of injury and recovery as well as development of fibrosis following i.p. injection of lipopolysaccharide (LPS) to corn oil-preloaded mice. Compared with mice receiving LPS alone, those receiving corn oil and LPS exhibited extended course of lung injury and repair that occurred over a period of >2 weeks instead of 3-5days. Importantly, LPS challenge of corn oil-preloaded mice resulted in pulmonary fibrosis during the repair phase as often seen in ARDS patients. In summary, this simple novel mouse model of ARDS could represent a valuable experimental tool to elucidate mechanisms that regulate lung injury and repair in ARDS patients.

Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

PubMed

Lichtman, Judith H; Froelicher, Erika S; Blumenthal, James A; Carney, Robert M; Doering, Lynn V; Frasure-Smith, Nancy; Freedland, Kenneth E; Jaffe, Allan S; Leifheit-Limson, Erica C; Sheps, David S; Vaccarino, Viola; Wulsin, Lawson

2014-03-25

Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. Writing group members were approved by the American Heart Association's Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.

A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.

PubMed

Farese, Ann M; Cohen, Melanie V; Katz, Barry P; Smith, Cassandra P; Jackson, William; Cohen, Daniel M; MacVittie, Thomas J

2012-10-01

The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management. A blinded, randomized study (n = 48 rhesus macaques) determined the lethal dose-response relationship using bilateral 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90 Gy at 0.80 Gy min(-1). Following irradiation, animals were monitored for complete bloodcounts, body weight, temperature, diarrhea, and hydration status for 60 d. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics, and nutrition. The primary endpoint was survival at 60 d post-irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents, and tissue histology. The study defined an LD30/60 of 7.06 Gy, LD50/60 of 7.52 Gy, and an LD70/60 of 7.99 Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.

Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury

DTIC Science & Technology

2017-07-01

glutamate from the brain. Scope: We will test this novel and powerful neuroprotective treatment in a rat model of repetitive mild (concussive) TBIs...variability. 2. Completed statistical analysis of behavioral experiments examining effects of rGOT and rGOT + OxAc on outcome on rotarod and Morris water ...neuroprotective treatment in a rat model of a single moderate TBI and in a rat model of repetitive mild (concussive) TBIs. Outcome measures include blood and

Iowa radon leukaemia study: a hierarchical population risk model for spatially correlated exposure measured with error.

PubMed

Smith, Brian J; Zhang, Lixun; Field, R William

2007-11-10

This paper presents a Bayesian model that allows for the joint prediction of county-average radon levels and estimation of the associated leukaemia risk. The methods are motivated by radon data from an epidemiologic study of residential radon in Iowa that include 2726 outdoor and indoor measurements. Prediction of county-average radon is based on a geostatistical model for the radon data which assumes an underlying continuous spatial process. In the radon model, we account for uncertainties due to incomplete spatial coverage, spatial variability, characteristic differences between homes, and detector measurement error. The predicted radon averages are, in turn, included as a covariate in Poisson models for incident cases of acute lymphocytic (ALL), acute myelogenous (AML), chronic lymphocytic (CLL), and chronic myelogenous (CML) leukaemias reported to the Iowa cancer registry from 1973 to 2002. Since radon and leukaemia risk are modelled simultaneously in our approach, the resulting risk estimates accurately reflect uncertainties in the predicted radon exposure covariate. Posterior mean (95 per cent Bayesian credible interval) estimates of the relative risk associated with a 1 pCi/L increase in radon for ALL, AML, CLL, and CML are 0.91 (0.78-1.03), 1.01 (0.92-1.12), 1.06 (0.96-1.16), and 1.12 (0.98-1.27), respectively. Copyright 2007 John Wiley & Sons, Ltd.

A Systematic Review of Music Therapy Practice and Outcomes with Acute Adult Psychiatric In-Patients

PubMed Central

Carr, Catherine; Odell-Miller, Helen; Priebe, Stefan

2013-01-01

Background and Objectives There is an emerging evidence base for the use of music therapy in the treatment of severe mental illness. Whilst different models of music therapy have been developed in mental health care, none have specifically accounted for the features and context of acute in-patient settings. This review aimed to identify how music therapy is provided for acute adult psychiatric in-patients and what outcomes have been reported. Review Methods A systematic review using medical, psychological and music therapy databases. Papers describing music therapy with acute adult psychiatric in-patients were included. Analysis utilised narrative synthesis. Results 98 papers were identified, of which 35 reported research findings. Open group work and active music making for nonverbal expression alongside verbal reflection was emphasised. Aims were engagement, communication and interpersonal relationships focusing upon immediate areas of need rather than longer term insight. The short stay, patient diversity and institutional structure influenced delivery and resulted in a focus on single sessions, high session frequency, more therapist direction, flexible use of musical activities, predictable musical structures, and clear realistic goals. Outcome studies suggested effectiveness in addressing a range of symptoms, but were limited by methodological shortcomings and small sample sizes. Studies with significant positive effects all used active musical participation with a degree of structure and were delivered in four or more sessions. Conclusions No single clearly defined model exists for music therapy with adults in acute psychiatric in-patient settings, and described models are not conclusive. Greater frequency of therapy, active structured music making with verbal discussion, consistency of contact and boundaries, an emphasis on building a therapeutic relationship and building patient resources may be of particular importance. Further research is required to develop specific music therapy models for this patient group that can be tested in experimental studies. PMID:23936399

Incidence Proportion of Acute Cor Pulmonale in Patients with Acute Respiratory Distress Syndrome Subjected to Lung Protective Ventilation: A Systematic Review and Meta-analysis.

PubMed

Das, Saurabh Kumar; Choupoo, Nang Sujali; Saikia, Priyam; Lahkar, Amitabh

2017-06-01

Reported incidence of acute cor pulmonale (ACP) in patients with acute respiratory distress syndrome (ARDS) varies from 10% to 84%, despite being subjected to lung protective ventilation according to the current guidelines. The objective of this review is to find pooled cumulative incidence of ACP in patients with ARDS undergoing lung protective ventilation. We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILACS, and WHO Clinical Trial Registry. Cross-sectional or cohort studies were included if they reported or provided data that could be used to calculate the incidence proportion of ACP. Inverse variance heterogeneity (IVhet) and random effect model were used for the main outcome and measures. We included 16 studies encompassing 1661 patients. The cumulative incidence of ACP using IVhet analysis was 23% (95% confidence interval [CI] = 18%-28%) over 3 days of lung protective ventilation. Random effect analysis of 7 studies (1250 patients) revealed pooled odd ratio of mortality of 1.16 (95% CI = 0.80-1.67, P = 0.44) due to ACP. Patients with ARDS have a 23% risk of developing ACP with lung protective ventilation. Findings of this review indicate the need of updating existing guidelines for ventilating ARDS patients to incorporate right ventricle protective strategy.

Machine learning for outcome prediction of acute ischemic stroke post intra-arterial therapy.

PubMed

Asadi, Hamed; Dowling, Richard; Yan, Bernard; Mitchell, Peter

2014-01-01

Stroke is a major cause of death and disability. Accurately predicting stroke outcome from a set of predictive variables may identify high-risk patients and guide treatment approaches, leading to decreased morbidity. Logistic regression models allow for the identification and validation of predictive variables. However, advanced machine learning algorithms offer an alternative, in particular, for large-scale multi-institutional data, with the advantage of easily incorporating newly available data to improve prediction performance. Our aim was to design and compare different machine learning methods, capable of predicting the outcome of endovascular intervention in acute anterior circulation ischaemic stroke. We conducted a retrospective study of a prospectively collected database of acute ischaemic stroke treated by endovascular intervention. Using SPSS®, MATLAB®, and Rapidminer®, classical statistics as well as artificial neural network and support vector algorithms were applied to design a supervised machine capable of classifying these predictors into potential good and poor outcomes. These algorithms were trained, validated and tested using randomly divided data. We included 107 consecutive acute anterior circulation ischaemic stroke patients treated by endovascular technique. Sixty-six were male and the mean age of 65.3. All the available demographic, procedural and clinical factors were included into the models. The final confusion matrix of the neural network, demonstrated an overall congruency of ∼ 80% between the target and output classes, with favourable receiving operative characteristics. However, after optimisation, the support vector machine had a relatively better performance, with a root mean squared error of 2.064 (SD: ± 0.408). We showed promising accuracy of outcome prediction, using supervised machine learning algorithms, with potential for incorporation of larger multicenter datasets, likely further improving prediction. Finally, we propose that a robust machine learning system can potentially optimise the selection process for endovascular versus medical treatment in the management of acute stroke.

Zebrafish as a model for acetylcholinesterase-inhibiting organophosphorus agent exposure and oxime reactivation

PubMed Central

Koenig, Jeffrey A.; Dao, Thuy L.; Kan, Robert K.; Shih, Tsung-Ming

2016-01-01

The current research progression efforts for investigating novel treatments for exposure to organophosphorus (OP) compounds that inhibit acetylcholinesterase (AChE), including pesticides and chemical warfare nerve agents (CWNAs), rely solely on in vitro cell assays and in vivo rodent models. The zebrafish (Danio rerio) is a popular, well-established vertebrate model in biomedical research that offers high-throughput capabilities and genetic manipulation not readily available with rodents. A number of research studies have investigated the effects of subacute developmental exposure to OP pesticides in zebrafish, observing detrimental effects on gross morphology, neuronal development, and behavior. Few studies, however, have utilized this model to evaluate treatments, such as oxime reactivators, anticholinergics, or anticonvulsants, following acute exposure. Preliminary work has investigated the effects of CWNA exposure. The results clearly demonstrated relative toxicity and oxime efficacy similar to that reported for the rodent model. This review surveys the current literature utilizing zebrafish as a model for OP exposure and highlights its potential use as a high-throughput system for evaluating AChE reactivator antidotal treatments to acute pesticide and CWNA exposure. PMID:27123828

Acute and chronic suppression of the central ghrelin signaling system reveals a role in food anticipatory activity.

PubMed

Verhagen, Linda A W; Egecioglu, Emil; Luijendijk, Mieneke C M; Hillebrand, Jacquelien J G; Adan, Roger A H; Dickson, Suzanne L

2011-05-01

Using the rodent activity-based anorexia (ABA) model that mimics clinical features of anorexia nervosa that include food restriction-induced hyperlocomotion, we found that plasma ghrelin levels are highly associated with food anticipatory behaviour, measured by running wheel activity in rats. Furthermore, we showed that ghrelin receptor (GHS-R1A) knockout mice do not anticipate food when exposed to the ABA model, unlike their wild type littermate controls. Likewise, food anticipatory activity in the ABA model was suppressed by a GHS-R1A antagonist administered either by acute central (ICV) injection to rats or by chronic peripheral treatment to mice. Interestingly, the GHS-R1A antagonist did not alter food intake in any of these models. Therefore, we hypothesize that suppression of the central ghrelin signaling system via GHS-R1A provides an interesting therapeutic target to treat hyperactivity in patients suffering from anorexia nervosa. Copyright © 2010. Published by Elsevier B.V.

Neuroimaging of the Wernicke–Korsakoff Syndrome

PubMed Central

Sullivan, Edith V.; Pfefferbaum, Adolf

2009-01-01

Aim: Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition. Methods: Neuropathology of KS detectable with MRI has a different neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance. Results: Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus, cerebellum and pons. The development and resolution of brain structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion. Conclusions: Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE. PMID:19066199

Neuroimaging of the Wernicke-Korsakoff syndrome.

PubMed

Sullivan, Edith V; Pfefferbaum, Adolf

2009-01-01

Presented is the neuroradiological signature of acute Wernicke's encephalopathy (WE), derived from different types of magnetic resonance imaging (MRI) sequences. WE results from thiamine depletion, and its most typical antecedent is chronic alcohol dependence. Brain regions observed with in vivo MRI affected in acute WE include the mammillary bodies, periaqueductal and periventricular gray matter, collicular bodies and thalamus. These affected areas are usually edematous and are best visualized and quantified with MRI sequences that highlight such tissue. Following the acute WE phase and resolution of edema and inflammation of affected brain tissue, WE, if not adequately treated with thiamine repletion, can herald Korsakoff's syndrome (KS), with its symptomatic hallmark of global amnesia, that is, the inability to commit newly encountered (episodic) information to memory for later recall or recognition. Neuropathology of KS detectable with MRI has a different neuroradiological signature from the acute stage and can be observed as tissue shrinkage or atrophy of selective brain structures, including the mammillary bodies and thalamus and ventricular expansion, probably indicative of atrophy of surrounding gray matter nuclei. Quantification of these and additional gray matter structures known to underlie global amnesia reveal substantial bilateral volume deficits in the hippocampus, in addition to the mammillary bodies and thalamus, and modest deficits in the medial septum/diagonal band of Broca. The infratentorium is also affected, exhibiting volume deficits in cerebellar hemispheres, anterior superior vermis and pons, contributing to ataxia of gait and stance. Consideration of WKS structural brain changes in the context of the neuropathology of non-WKS alcoholism revealed a graded pattern of volume deficits, from mild in non-WKS alcoholics to moderate or severe in WKS, in the mammillary bodies, hippocampus, thalamus, cerebellum and pons. The development and resolution of brain structures affected in acute, chronic and treated WE was verified in longitudinal MRI study of rats that modeled of the interaction of extensive alcohol consumption and thiamine depletion and repletion. Thus, neuroradiological examination with MRI is valuable in the diagnosis of acute WE and enables in vivo tracking of the progression of the brain pathology of WE from the acute pathological phase to resolution with thiamine treatment or to progression to KS without treatment. Further, in vivo MRI facilitates translational studies to model antecedent conditions contributing to the development, sequelae and treatment of WE.

Determinants of Emergency Medical Services Utilization Among Acute Ischemic Stroke Patients in Hubei Province in China.

PubMed

Yin, Xiaoxv; Yang, Tingting; Gong, Yanhong; Zhou, Yanfeng; Li, Wenzhen; Song, Xingyue; Wang, Mengdie; Hu, Bo; Lu, Zuxun

2016-03-01

Emergency medical services (EMS) can effectively shorten the prehospital delay for patients with acute ischemic stroke. This study aimed to investigate EMS utilization and its associated factors in patients with acute ischemic stroke in China. A cross-sectional study was conducted from October 1, 2014, to January 31, 2015, which included 2096 patients admitted for acute ischemic stroke from 66 hospitals in Hubei province in China. A multivariable stepwise logistic regression model was undertaken to identify the factors associated with EMS utilization. Of the 2096 participants, only 323 cases (15.4%) used EMS. Those acute ischemic stroke patients who previously used EMS (odds ratio [OR] =9.8), whose National Institutes of Health Stroke Scale score was ≥10 (OR=3.7), who lived in urban communities (OR=2.5), who had sudden onset of symptoms (OR=2.4), who experienced their first stroke (OR=1.8), and who recognized initial symptom as stroke (OR=1.4) were more likely to use EMS. Additionally, when acute ischemic stroke patients' stroke symptom were noticed first by others (OR=2.1), rather than by the patients, EMS was more likely to be used. A very low proportion of patients with acute ischemic stroke used the EMS in Hubei province in China. Considerable education programs are required regarding knowledge of potential symptoms and the importance of EMS for stroke. © 2016 American Heart Association, Inc.

Management and Outcomes of Acute Surgical Patients at a District Hospital in Uganda with Non-physician Emergency Clinicians.

PubMed

Dresser, Caleb; Periyanayagam, Usha; Dreifuss, Brad; Wangoda, Robert; Luyimbaazi, Julius; Bisanzo, Mark

2017-09-01

Acute surgical care services in rural Sub-Saharan Africa suffer from human resource and systemic constraints. Developing emergency care systems and task sharing aspects of acute surgical care addresses many of these issues. This paper investigates the degree to which specialized non-physicians practicing in a dedicated Emergency Department contribute to the effective and efficient management of acute surgical patients. This is a retrospective review of an electronic quality assurance database of patients presenting to an Emergency Department in rural Uganda staffed by non-physician clinicians trained in emergency care. Relevant de-identified clinical data on patients admitted directly to the operating theater from 2011 to 2014 were analyzed in Microsoft Excel. Overall, 112 Emergency Department patients were included in the analysis and 96% received some form of laboratory testing, imaging, medication, or procedure in the ED, prior to surgery. 72% of surgical patients referred by ED received preoperative antibiotics, and preoperative fluid resuscitation was initiated in 65%. Disposition to operating theater was accomplished within 3 h of presentation for 73% of patients. 79% were successfully followed up to assess outcomes at 72 h. 92% of those with successful follow-up reported improvement in their clinical condition. The confirmed mortality rate was 5%. Specialized non-physician clinicians practicing in a dedicated Emergency Department can perform resuscitation, bedside imaging and laboratory studies to aid in diagnosis of acute surgical patients and arrange transfer to an operating theater in an efficient fashion. This model has the potential to sustainably address structural and human resources problems inherent to Sub-Saharan Africa's current acute surgical care model and will benefit from further study and expansion.

A prospective cohort study on the association between coffee drinking and risk of non-gallstone-related acute pancreatitis.

PubMed

Oskarsson, Viktor; Sadr-Azodi, Omid; Orsini, Nicola; Wolk, Alicja

2016-05-28

Only one previous study has examined the association between coffee consumption and risk of acute pancreatitis, and it found a reduced risk for alcohol-related episodes among high consumers of coffee. Therefore, we examined (1) the association between coffee consumption and risk of non-gallstone-related acute pancreatitis and (2) whether this association was modified by alcohol intake. Data were obtained from two prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, including 76 731 men and women (born 1914-1952). Coffee consumption was assessed at baseline with a FFQ, and the cohorts were followed up between 1998 and 2012 via linkage to national health registries. Hazard ratios were estimated using Cox models, with adjustment for potential confounding factors. During 1 035 881 person-years of total follow-up, 383 cases (246 in men and 137 in women) of incident non-gallstone-related acute pancreatitis were identified. Overall, and irrespective of whether a categorical or a continuous exposure model was used, we observed no association between coffee consumption and risk of non-gallstone-related acute pancreatitis (e.g. the multivariable-adjusted hazard ratio for each 1 cup/d increase in coffee consumption was 0·97; 95 % CI 0·92, 1·03). There was no evidence of effect modification by alcohol intake (P interaction=0·77). In conclusion, coffee consumption was not associated with risk of non-gallstone-related acute pancreatitis in this large prospective cohort study. Because of the limited number of epidemiological studies and their conflicting results, further research is needed to elucidate this potential association.

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

PubMed

Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

2016-01-01

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

2015-01-01

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are a documented concern for human exploration of space. Acute CNS risks include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

In vivo regulation of the heme oxygenase-1 gene in humanized transgenic mice

PubMed Central

Kim, Junghyun; Zarjou, Abolfazl; Traylor, Amie M.; Bolisetty, Subhashini; Jaimes, Edgar A.; Hull, Travis D.; George, James F.; Mikhail, Fady M.; Agarwal, Anupam

2012-01-01

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation producing equimolar amounts of carbon monoxide, iron, and biliverdin. Induction of HO-1 is a beneficial response to tissue injury in diverse animal models of diseases including acute kidney injury. In vitro analysis has shown that the human HO-1 gene is transcriptionally regulated by changes in chromatin conformation but whether such control occurs in vivo is not known. To enable such analysis, we generated transgenic mice, harboring an 87-kb bacterial artificial chromosome expressing human HO-1 mRNA and protein and bred these mice with HO-1 knockout mice to generate humanized BAC transgenic mice. This successfully rescued the phenotype of the knockout mice including reduced birth rates, tissue iron overload, splenomegaly, anemia, leukocytosis, dendritic cell abnormalities and survival after acute kidney injury induced by rhabdomyolysis or cisplatin nephrotoxicity. Transcription factors such as USF1/2, JunB, Sp1, and CTCF were found to associate with regulatory regions of the human HO-1 gene in the kidney following rhabdomyolysis. Chromosome Conformation Capture and ChIP-loop assays confirmed this in the formation of chromatin looping in vivo. Thus, these bacterial artificial chromosome humanized HO-1 mice are a valuable model to study the human HO-1 gene providing insight to the in vivo architecture of the gene in acute kidney injury and other diseases. PMID:22495295

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

PubMed Central

Zhan, Xianbao; Wang, Fan; Bi, Yan

2016-01-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

Ultraviolet Radiation: Human Exposure and Health Risks.

ERIC Educational Resources Information Center

Tenkate, Thomas D.

1998-01-01

Provides an overview of human exposure to ultraviolet radiation and associated health effects as well as risk estimates for acute and chronic conditions resulting from such exposure. Demonstrates substantial reductions in health risk that can be achieved through preventive actions. Also includes a risk assessment model for skin cancer. Contains 36…

The effect of donepezil on the cognitive ability early in the course of recovery from traumatic brain injury.

PubMed

Campbell, Kelsey A; Kennedy, Richard E; Brunner, Robert C; Hollis, Sean D; Lumsden, Ross A; Novack, Thomas A

2018-05-08

To investigate the effect of donepezil on cognitive ability in patients who have sustained a traumatic brain injury (TBI). We hypothesized that donepezil, an acetylcholinesterase inhibitor, would enhance cognitive recovery beyond that of usual care in an acute rehabilitation facility. This retrospective, longitudinal analysis included 55 patients who were non-randomly prescribed donepezil during acute care and compared them to 74 patients who received usual rehabilitation treatment. All 129 patients completed neuropsychological assessment at two time points. Donepezil was increased from 5 to 10 mg 7-10 days after initiation and maintained until follow-up cognitive assessment. Primary cognitive abilities of interest included processing speed, attention and memory. Cognitive and functional abilities were assessed by a standard neuropsychological battery for TBI. Propensity scores were used to adjust for differences between groups. Mixed effect model analysis showed no significant differences between treatment and control groups on all neuropsychological subtests over time. Acute administration of donepezil did not significantly improve measures of cognitive or functional ability beyond that of treatment as usual in patients with moderate-to-severe TBI.

Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link.

PubMed

Ghoshal, Uday C; Gwee, Kok-Ann

2017-07-01

Evidence is emerging that IBS, a hitherto enigmatic disorder thought to be predominantly related to psychological factors, has a microorganic basis in a subset of patients with the disease. Post-infectious IBS (PI-IBS), commonly of the diarrhoea-predominant subtype (defined as new development of IBS following acute infectious diarrhoea), is one such condition known to occur in up to 10-30% individuals after acute gastroenteritis. However, following acute infectious gastroenteritis, patients can also develop post-infectious malabsorption syndrome (PI-MAS), popularly known as tropical sprue. As no study on PI-IBS has rigorously excluded tropical sprue by appropriate investigations, including small intestinal biopsy, the frequency of tropical sprue among patients with PI-IBS is not known. Small intestinal bacterial overgrowth (SIBO) has been suggested to be associated with IBS in general, and in particular diarrhoea-predominant IBS, including PI-IBS. SIBO is also known to be associated with tropical sprue. As both IBS, particularly the subset probably associated with SIBO, and tropical sprue improve with antibiotic treatment, we provide evidence and an explanatory model to support a link among these disorders.

Predicting the clinical manifestations in necrotizing acute pancreatitis patients with splanchnic vein thrombosis.

PubMed

Zhou, Jing; Ke, Lu; Yang, Dongliang; Chen, Yizhe; Li, Gang; Tong, Zhihui; Li, Weiqin; Li, Jieshou

Splanchnic venous thrombosis (SVT) is a relatively rare but important complication of necrotizing acute pancreatitis (NAP). Clinical manifestations and severity of this complication in different patients vary greatly, ranging from mild abdominal discomfort even asymptomatic to lethal gastrorrhagia or hepatic failure. The aim of the present study was to develop a model to predict the clinical manifestations of SVT in NAP patients. This retrospective cohort study was conducted in the surgical intensive care unit (SICU) of Jinling Hospital. Patients with the presence of both pancreatic necrosis and SVT were selected for possible inclusion. Both univariate and multivariate logistic regression analyses were applied using 12 indices including age, gender, Acute Physiology and Chronic Health Evaluation II scores (APACHE II), CRP(C - reactive protein) levels, etc to assess potential predictors for symptomatic pancreatic splanchnic venous thrombosis (PSVT) in this cohort. A prognostic nomogram was also applied to develop an easy-to-use prediction model. A total of 104 patients with necrotizing acute pancreatitis (NAP) and splanchnic vein thrombosis (SVT) from January 2012 to December 2013 were enrolled for analysis. A quarter of study subjects (26 of 104, 25%) developed variable symptomatic manifestations including variceal bleeding, persistent ascites and enteral nutrition (EN) intolerance during the disease course. In the multivariable regression model, the following factors were found to be associated with the occurrence of symptomatic SVT: Balthazar's computed tomography (CT) score (OR = 1.818; 95% CI: 1.251-2.641; P = 0.002), intra-abdominal pressure (IAP) (OR = 1.172; 95% CI: 1.001-1.251; P = 0.043 and presence of SMVT (OR = 6.946; 95% CI: 2.290-21.074; P = 0.001). A prediction model incorporating these factors demonstrated an area under the receiver operating characteristic curve of 0.842. Balthazar's CT score, IAP and SMVT are predictors of symptomatic SVT in NAP patients. The nomogram we conducted can be used as an easy-to-use risk stratification tool in either clinical practice or future studies. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups

PubMed Central

Pulte, Dianne; Redaniel, Maria Theresa; Jansen, Lina; Brenner, Hermann; Jeffreys, Mona

2013-01-01

The survival of younger patients with acute leukemia has improved in the early 21st century, but it is unknown whether people of all ethnic and racial backgrounds have benefited equally. Using cancer registry data from the Surveillance, Epidemiology and End Results Program, we assessed trends in 5-year relative survival for patients aged 15 years or more with acute lymphoblastic leukemia and acute myeloblastic leukemia divided by racial and ethnic group, including non-Hispanic whites, African-Americans, Hispanics, and Asian-Pacific Islanders in the 1990s and the early 21st century. Modeled period analysis was used to obtain the most up-to-date estimates of survival. Overall, the 5-year survival increased from 31.6% in 1997-2002 to 39.0% in 2003-2008 for patients with acute lymphoblastic leukemia and from 15.5% in 1991-1996 to 22.5% in 2003-2008 for those with acute myeloblastic leukemia. Nevertheless, among patients with acute lymphoblastic leukemia, age-adjusted 5-year relative survival rates remained lower for African-Americans and Hispanics than for non-Hispanic whites. Among patients with acute myeloblastic leukemia, the increase in survival was greatest (from 32.6% in 1991-1996 to 47.1% in 2003-2008) for younger patients (15-54 years), and was more pronounced for non-Hispanic whites (+16.4% units) than for other patients (+10.8% units). Increases in survival are observed in all ethnic or racial groups. Nevertheless, among patients with acute leukemias, disparities in survival persist between non-Hispanic white people and people of other ethnic or racial groups. Disparities are increasing in younger patients with acute myeloblastic leukemia. Improvements in access to treatment, especially for minority patients, may improve outcomes. PMID:22929974

Late Intensive Care Unit Admission in Liver Transplant Recipients: 10-Year Experience.

PubMed

Atar, Funda; Gedik, Ender; Kaplan, Şerife; Zeyneloğlu, Pınar; Pirat, Arash; Haberal, Mehmet

2015-11-01

We evaluated late intensive care unit admission in liver transplant recipients to identify incidences and causes of acute respiratory failure in the postoperative period and to compare these results with results in patients who did not have acute respiratory failure. We retrospectively screened the data of 173 consecutive adult liver transplant recipients from January 2005 through March 2015 to identify patients with late admission (> 30 d posttransplant) to an intensive care unit. Patients were divided into 2 groups: patients with and without acute respiratory failure. Acute respiratory failure was defined as severe dyspnea, respiratory distress, decreased oxygen saturation, hypoxemia or hypercapnia on room air, or need for noninvasive or invasive mechanical ventilation. Demographic, laboratory, clinical, and respiratory data were collected. Model for End-Stage Liver Disease, Acute Physiology and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores; lengths of intensive care unit and hospital stays; and hospital mortality were assessed. Among 173 patients, 37 (21.4%) were admitted to an intensive care unit, including 22 (59.5%) with acute respiratory failure. The leading cause of acute respiratory failure was pneumonia (n = 19, 86.4%). Patients with acute respiratory failure had significantly lower levels of albumin before intensive care unit admission (P = .003). In patients with acute respiratory failure, severe sepsis and septic shock were more frequently observed and tracheotomy was more frequently performed (P = .041). Acute respiratory failure developed in 59.5% of liver transplant recipients with late intensive care unit admission. The leading cause was pneumonia, with this group of patients having higher requirements for invasive mechanical ventilation and tracheotomy, longer stays in an intensive care unit, and higher mortality.

Integrating microRNAs into a system biology approach to acute lung injury.

PubMed

Zhou, Tong; Garcia, Joe G N; Zhang, Wei

2011-04-01

Acute lung injury (ALI), including the ventilator-induced lung injury (VILI) and the more severe acute respiratory distress syndrome (ARDS), are common and complex inflammatory lung diseases potentially affected by various genetic and nongenetic factors. Using the candidate gene approach, genetic variants associated with immune response and inflammatory pathways have been identified and implicated in ALI. Because gene expression is an intermediate phenotype that resides between the DNA sequence variation and the higher level cellular or whole-body phenotypes, the illustration of gene expression regulatory networks potentially could enhance understanding of disease susceptibility and the development of inflammatory lung syndromes. MicroRNAs (miRNAs) have emerged as a novel class of gene regulators that play critical roles in complex diseases including ALI. Comparisons of global miRNA profiles in animal models of ALI and VILI identified several miRNAs (eg, miR-146a and miR-155) previously implicated in immune response and inflammatory pathways. Therefore, via regulation of target genes in these biological processes and pathways, miRNAs potentially contribute to the development of ALI. Although this line of inquiry exists at a nascent stage, miRNAs have the potential to be critical components of a comprehensive model for inflammatory lung disease built by a systems biology approach that integrates genetic, genomic, proteomic, epigenetic as well as environmental stimuli information. Given their particularly recognized role in regulation of immune and inflammatory responses, miRNAs also serve as novel therapeutic targets and biomarkers for ALI/ARDS or VILI, thus facilitating the realization of personalized medicine for individuals with acute inflammatory lung disease. Copyright © 2011 Mosby, Inc. All rights reserved.

Acute kidney injury post-major orthopaedic surgery: A single-Centre case-control study.

PubMed

Ying, Tracey; Chan, Samantha; Lane, Stephen; Somerville, Christine

2018-02-01

To identify risk factors for acute kidney injury following major orthopaedic surgery. We included all patients undergoing major orthopaedic surgery at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188 surgeries audited, we identified cases of acute kidney injury using the RIFLE criteria and matched those to controls 2:1 for age, sex, procedure and chronic kidney disease stage. We reviewed their records for risk factors of postoperative acute kidney injury, including medications such as gentamicin, diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. We reviewed the patients' history of cardiovascular disease, chronic liver disease, hypertension and diabetes mellitus along with presence of sepsis and obesity. Associations of hypothetical risk factors were estimated using conditional logistic regression. We identified 164 cases of AKI in an elderly cohort (median age = 73 years). Controlling for baseline comorbidities, both diuretic and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use were found to be associated with a twofold risk of acute kidney injury (diuretic - OR 2.06 95% CI:1.30-3.26, P < 0.005, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use OR 2.09 95% CI:1.31-3.32, P < 0.005). A dose-effect model accounting for perioperative nonsteroidal anti-inflammatory drug administration demonstrated a linear relationship between the number of times these drugs were given and postoperative acute kidney injury risk (OR 1.35 95% CI:1.05-1.73, P = 0.02). We identified perioperative diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to be significantly associated with postoperative AKI. Further prospective studies are required to confirm this. © 2016 Asian Pacific Society of Nephrology.

Abrupt opium discontinuation has no significant triggering effect on acute myocardial infarction.

PubMed

Masoomi, Mohammad; Zare, Jahangir; Nasri, Hamidreza; Mirzazadeh, Ali; Sheikhvatan, Mehrdad

2011-04-01

A deleterious effect of withdrawal symptoms due to abrupt discontinuation of opium on the cardiovascular system is one of the recent interesting topics in the cardiovascular field. The current study hypothesized that the withdrawal syndrome due to discontinuing opium might be an important trigger for the appearance of acute myocardial infarction. Eighty-one opium-addicted individuals who were candidates for cardiovascular clinical evaluation and consecutively hospitalized in the coronary care unit (CCU) ward of Shafa Hospital in Kerman between January and July 2009 were included in the study and categorized in the case group, including patients experiencing withdrawal symptoms within 6-12 h after the reduced or discontinued use of opium according to the Diagnostic and Statistical Manual of Mental Disorders-revised IV version (DSM-IV-R) criteria for opium dependence and withdrawal, and the control group, without opium withdrawal symptoms. The appearance of acute myocardial infarction was compared between the two groups using multivariable regression models. Acute myocardial infarction occurred in 50.0% of those with withdrawal symptoms and in 45.1% of patients without evidence of opium withdrawal (P = 0.669). Multivariable analysis showed that opium withdrawal symptoms were not a trigger for acute myocardial infarction adjusting for demographic characteristics, marital status, education level and common coronary artery disease risk profiles [odds ratio (OR) = 0.920, 95% confidence interval (CI) = 0.350-2.419, P = 0.866]. Also, daily dose of opium before reducing or discontinuing use did not predict the appearance of myocardial infarction in the presence of confounder variables (OR = 0.975, 95% CI = 0.832-1.143, P = 0.755). Withdrawal syndrome due to abrupt discontinuation of opium does not have a triggering role for appearance of acute myocardial infarction.

[The affect of Erigeron Breviscapus (Vant.) Hand-Mazz on axoplasmic transport of optic nerve in rats with experimentally elevated intraocular pressure].

PubMed

Zhu, Y; Jiang, Y; Liu, Z; Luo, X; Wu, Z

2000-07-01

To investigate whether Erigeron Breviscapus (Vant.) Hand-Mazz (EBHM) can improve the optic nerve axoplasmic transport in rats with experimentally elevated intraocular pressure (IOP). Thirty healthy SD rats were used for the study, acute elevated IOP model in the right eye was built, then they were divided into three groups randomly: Group A (0 day group) included six rats for retinal ganglion cell (RGC) counting via left superior colliculus retrograde horse radish perokidase labeling; Group B, twelve rats divided into EBHM treatment group and control group (6 rats in each subgroup) for RGC counting via left superior colliculus retrograde labeling after twenty days, and Group C included twelve rats submitted the same treatment and procedure as group B after 40 days. After 0 day of acute elevated IOP, no labeled RGCs were observed. After twenty days of acute elevated IOP, in the control and EBHM subgroups the density of labeled RGCs were (423 +/- 220)/mm(2) and (749 +/- 294)/mm(2) respectively, the difference between two subgroups showed statistical significance (P < 0.01). After 40 days of acute elevated IOP, the density of RGCs in the control and EBHM subgroups in group C were (610 +/- 315)/mm(2) and (1,048 +/- 393)/mm(2) respectively, the difference between the two subgroups being statistically significant (P < 0.01). After 20 days and 40 days of acute elevation of IOP, the density of RGCs is obviously higher in EBHM group than that in the control group. It is revealed that EBHM can improve the optic nerve axoplasmic transportation blocked by acute elevation of IOP in rats.

[Hospital at home: assessment of early discharge in terms of patients mortality and satisfaction].

PubMed

Damiani, G; Pinnarelli, L; Ricciardi, G

2006-01-01

New organizational models are essentials for European Hospitals because of restraining budget and ageing of population. Hospital at home is an alternative to inpatient care, effective both in clinical and economic ground. The aim of our study was to evaluate the impact of Hospital at Home in terms of decreased mortality and patient satisfaction. We carried out a meta-analysis of the literature about hospital at home interventions. We searched Medline (to December 2002), the Cochrane Controlled Trials Register (to October 2002) and other bibliographical databases, with a supplementary handsearching of literature. We used the following keywords: hospital at home, home hospitalization, mortality, patient satisfaction, cost, acute hospital care, conventional hospitalization. We included studies respecting the following criteria: analytical or experimental studies aimed at compare early discharge to hospital at home and continued care in an acute hospital. Review Manager 4.2 software was used to collect data and perform statistical analysis. We found 2420 articles searching for the chosen keywords. Twelve studies (2048 patients) were included for death outcome and six studies (1382 patients) were included for satisfaction outcome. The selected studies indicated a greater effect size of patient satisfaction in home patients than hospitalized ones (Odds Ratio: 1.58 95% CI: 1.25, 2.00) and showed no difference in terms of mortality (Risk Difference: -0.01 95% CI: -0.03, 0.02). Our results underline the effectiveness of this organizational model, as an alternative to continued care in an acute hospital. Further useful considerations could be drawn by economic evaluation studies carried out on field.

Reassessment of HIV-1 Acute Phase Infectivity: Accounting for Heterogeneity and Study Design with Simulated Cohorts

PubMed Central

Bellan, Steve E.; Dushoff, Jonathan; Galvani, Alison P.; Meyers, Lauren Ancel

2015-01-01

Background The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. Methods and Findings We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (d acute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0.79–57) and d acute = 1.7 mo (95% CrI: 0.55–6.8). The wide credibility intervals reflect an inability to distinguish a long, mildly infectious acute phase from a short, highly infectious acute phase, given the 10-mo Rakai observation intervals. The total additional risk, measured as excess hazard-months attributable to the acute phase (EHMacute) can be estimated more precisely: EHMacute = (RHacute - 1) × d acute, and should be interpreted with respect to the 120 hazard-months generated by a constant untreated chronic phase infectivity over 10 y of infection. From the Rakai data, we estimated that EHMacute = 8.4 (95% CrI: -0.27 to 64). This estimate is considerably lower than previously published estimates, and consistent with our independent estimate from viral load trajectories, 5.6 (95% confidence interval: 3.3–9.1). We found that previous overestimates likely stemmed from failure to account for risk heterogeneity and bias resulting from the retrospective cohort study design. Our results reflect the interaction between the retrospective cohort exclusion criteria and high (47%) rates of censorship amongst incident serodiscordant couples in the Rakai study due to loss to follow-up, couple dissolution, or study termination. We estimated excess physiological infectivity during the acute phase from couples data, but not the proportion of transmission attributable to the acute phase, which would require data on the broader population's sexual network structure. Conclusions Previous EHMacute estimates relying on the Rakai retrospective cohort data range from 31 to 141. Our results indicate that these are substantial overestimates of HIV-1 acute phase infectivity, biased by unmodeled heterogeneity in transmission rates between couples and by inconsistent censoring. Elevated acute phase infectivity is therefore less likely to undermine TasP interventions than previously thought. Heterogeneity in infectiousness and susceptibility may still play an important role in intervention success and deserves attention in future analyses PMID:25781323

Is mother-child transmission a possible vehicle for xylitol prophylaxis in acute otitis media?

PubMed

Danhauer, Jeffrey L; Kelly, Allison; Johnson, Carole E

2011-10-01

Xylitol can be a prophylaxis for acute otitis media (AOM), especially when administered via chewing gum, but that vehicle has limitations for children. This review sought evidence for links of mother-child transmission of bacteria and as a vehicle for xylitol as a prophylaxis for dental caries and its translation to AOM in infants and young children. Qualitative systematic review. Combining output from 43 search strings used earlier and submitting 20 new strings to PubMed resulted in 14 studies (six were excluded; eight were included). Included studies had to be published in English-language, peer-reviewed journals; involve mothers using xylitol; and assess bacteria or caries in their children. Evaluation forms were completed for search, retrieval, and quality assessment of included studies. The studies showed that mothers' chewing xylitol gum was a prophylaxis against bacteria and caries in their children. A mother-child transmission model was presented as a possible vehicle for use in comprehensive prevention programs for AOM. Potential for xylitol use to prevent AOM warrants further study. A mother-child model may apply to AOM for transmission of bacteria and as a prophylaxis, but alternative vehicles like nasal sprays should be investigated for ease of use and effectiveness.

Gamma-Terpinene Modulates Acute Inflammatory Response in Mice.

PubMed

Ramalho, Theresa Raquel de Oliveira; Oliveira, Maria Talita Pacheco de; Lima, Ana Luisa de Araujo; Bezerra-Santos, Claudio Roberto; Piuvezam, Marcia Regina

2015-09-01

The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this study was to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gamma-terpinene displayed reduced paw edema induced by carrageenan from 1-24 h after challenge. A similar reduction was observed when gamma-terpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophil migration as well as the production of interleukin-1β and tumor necrosis factor-α when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma-terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties. Georg Thieme Verlag KG Stuttgart · New York.

Clinical and pathologic changes in a guinea pig aerosol challenge model of acute Q fever.

PubMed

Russell-Lodrigue, K E; Zhang, G Q; McMurray, D N; Samuel, J E

2006-11-01

Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10(1) to 10(6) organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.

Cost-effectiveness of a novel blood-pool contrast agent in the setting of chest pain evaluation in an emergency department.

PubMed

Espinosa, Gabriela; Annapragada, Ananth

2013-10-01

We evaluated three diagnostic strategies with the objective of comparing the current standard of care for individuals presenting acute chest pain and no history of coronary artery disease (CAD) with a novel diagnostic strategy using an emerging technology (blood-pool contrast agent [BPCA]) to identify the potential benefits and cost reductions. A decision analytic model of diagnostic strategies and outcomes using a BPCA and a conventional agent for CT angiography (CTA) in patients with acute chest pain was built. The model was used to evaluate three diagnostic strategies: CTA using a BPCA followed by invasive coronary angiography (ICA), CTA using a conventional agent followed by ICA, and ICA alone. The use of the two CTA-based triage tests before ICA in a population with a CAD prevalence of less than 47% was predicted to be more cost-effective than ICA alone. Using the base-case values and a cost premium for BPCA over the conventional CT agent (cost of BPCA ≈ 5× that of a conventional agent) showed that CTA with a BPCA before ICA resulted in the most cost-effective strategy; the other strategies were ruled out by simple dominance. The model strongly depends on the rates of complications from the diagnostic tests included in the model. In a population with an elevated risk of contrast-induced nephropathy (CIN), a significant premium cost per BPCA dose still resulted in the alternative whereby CTA using BPCA was more cost-effective than CTA using a conventional agent. A similar effect was observed for potential complications resulting from the BPCA injection. Conversely, in the presence of a similar complication rate from BPCA, the diagnostic strategy of CTA using a conventional agent would be the optimal alternative. BPCAs could have a significant impact in the diagnosis of acute chest pain, in particular for populations with high incidences of CIN. In addition, a BPCA strategy could garner further savings if currently excluded phenomena including renal disease and incidental findings were included in the decision model.

Developing a Sustainable Need-Based Pediatric Acute Care Training Curriculum in Solomon Islands.

PubMed

Yu, Daniel Ta Yo; Gillon, Jason T; Dickson, Raymond; Schneider, Karen A; Stevens, Martha W

2017-01-01

The Johns Hopkins Hospital Pediatric Emergency Department (PED) was invited to collaborate with the National Referral Hospital (NRH), Solomon Islands, to establish an acute care pediatric education program for the country's inaugural class of national medical graduate trainees. To develop and evaluate a sustainable, need-based post-graduate training curriculum in pediatric acute care, resuscitation, and point-of-care ultrasound. A need-based training curriculum was developed utilizing the ADDIE model and was implemented and revised over the course of 2 years and two site visits. Implementation followed a train-the-trainer model. The curriculum consisted of high-yield didactics including workshops, simulations, hands-on ultrasound sessions, and lectures at the NRH. A mixed-methods design was used to evaluate the curriculum, including pre/posttesting, qualitative group discussions, and individual surveys. The curriculum was revised in response to ongoing learner evaluations and needs assessments. Continuing educational sessions after the site visit demonstrated sustainability. The curriculum included 19 core topics with 42 teaching sessions during the two site visits. A total of 135 pre/posttests and 366 individual surveys were collected from 46 trainees. Completion rates were 78.2% for surveys and 71.3% for pre/posttests. Pre/posttest scores increased from 44 to 63% during the first site visit and 69.6 to 77.6% during the second. Learners reported a mean 4.81/5 on a standard Likert scale for curriculum satisfaction. Group discussions and surveys highlighted key areas of knowledge growth, important clinical care advances, and identified further needs. Initial sustainability was demonstrated by continued ultrasound sessions led by local graduate trainees. A collaborative team including Johns Hopkins PED staff, Solomon Islands' graduate trainees, and NRH administration initiated a professional education curriculum for the first class of Solomon Islands' medical graduates. Knowledge growth and positive impacts of the program were reflected in learner survey and test scores. Graduate trainees were identified as local champions to continue as course instructors. This innovative curriculum was developed, revised, and initially sustained on site. It has been successful in introducing life-saving pediatric acute care and graduate training in Solomon Islands.

Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy.

PubMed

Wijsman, Robin; Dankers, Frank; Troost, Esther G C; Hoffmann, Aswin L; van der Heijden, Erik H F M; de Geus-Oei, Lioe-Fee; Bussink, Johan

2015-10-01

The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to distinct dosimetric characteristics of intensity-modulated radiation therapy (IMRT), 3D-CRT based models need revision. We established a multivariable NTCP model for AET in 149 AS-NSCLC patients undergoing IMRT. An established model selection procedure was used to develop an NTCP model for Grade ⩾2 AET (53 patients) including clinical and esophageal dose-volume histogram parameters. The NTCP model predicted an increased risk of Grade ⩾2 AET in case of: concurrent chemoradiotherapy (CCR) [adjusted odds ratio (OR) 14.08, 95% confidence interval (CI) 4.70-42.19; p<0.001], increasing mean esophageal dose [Dmean; OR 1.12 per Gy increase, 95% CI 1.06-1.19; p<0.001], female patients (OR 3.33, 95% CI 1.36-8.17; p=0.008), and ⩾cT3 (OR 2.7, 95% CI 1.12-6.50; p=0.026). The AUC was 0.82 and the model showed good calibration. A multivariable NTCP model including CCR, Dmean, clinical tumor stage and gender predicts Grade ⩾2 AET after IMRT for AS-NSCLC. Prior to clinical introduction, the model needs validation in an independent patient cohort. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A systematic review of advance practice providers in acute care: options for a new model in a burn intensive care unit.

PubMed

Edkins, Renee E; Cairns, Bruce A; Hultman, C Scott

2014-03-01

Accreditation Council for Graduate Medical Education mandated work-hour restrictions have negatively impacted many areas of clinical care, including management of burn patients, who require intensive monitoring, resuscitation, and procedural interventions. As surgery residents become less available to meet service needs, new models integrating advanced practice providers (APPs) into the burn team must emerge. We performed a systematic review of APPs in critical care questioning, how best to use all providers to solve these workforce challenges? We performed a systematic review of PubMed, CINAHL, Ovid, and Google Scholar, from 2002 to 2012, using the key words: nurse practitioner, physician assistant, critical care, and burn care. After applying inclusion/exclusion criteria, 18 relevant articles were selected for review. In addition, throughput and financial models were developed to examine provider staffing patterns. Advanced practice providers in critical care settings function in various models, both with and without residents, reporting to either an intensivist or an attending physician. When APPs participated, patient outcomes were similar or improved compared across provider models. Several studies reported considerable cost-savings due to decrease length of stay, decreased ventilator days, and fewer urinary tract infections when nurse practitioners were included in the provider mix. Restrictions in resident work-hours and changing health care environments require that new provider models be created for acute burn care. This article reviews current utilization of APPs in critical care units and proposes a new provider model for burn centers.

20180311 - Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development (SOT)

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

Aphasia As a Predictor of Stroke Outcome.

PubMed

Lazar, Ronald M; Boehme, Amelia K

2017-09-19

Aphasia is a common feature of stroke, affecting 21-38% of acute stroke patients and an estimated 1 million stroke survivors. Although stroke, as a syndrome, is the leading cause of disability in the USA, less is known about the independent impact of aphasia on stroke outcomes. During the acute stroke period, aphasia has been found to increase length of stay, inpatient complications, overall neurological disability, mortality, and to alter discharge disposition. Outcomes during the sub-acute and chronic stroke periods show that aphasia is associated with lower Functional Independence Measures (FIM) scores, longer stays in rehabilitation settings, poorer function in activities of daily living, and mortality. Factors that complicate the analysis of aphasia on post-stroke outcomes, however, include widely different systems of care across international settings that result in varying admission patterns to acute stroke units, allowable length of stays based on reimbursement, and criteria for rehabilitation placement. Aphasia arising from stroke is associated with worse outcomes both in the acute and chronic periods. Future research will have to incorporate disparate patterns in analytic models, and to take into account specific aphasia profiles and evolving methods of post-stroke speech-language therapy.

A novel neuroimaging model to predict early neurological deterioration after acute ischemic stroke.

PubMed

Huang, Yen-Chu; Tsai, Yuan-Hsiung; Lee, Jiann-Der; Yang, Jen-Tsung; Pan, Yi-Ting

2018-05-16

In acute ischemic stroke, early neurological deterioration (END) may occur in up to one-third of patients. However, there is still no satisfying or comprehensive predictive model for all the stroke subtypes. We propose a practical model to predict END using magnetic resonance imaging (MRI). Patients with anterior circulation infarct were recruited and they underwent an MRI within 24 hours of stroke onset. END was defined as an elevation of ≥2 points on the National Institute of Health Stroke Scale (NIHSS) within 72 hours of stroke onset. We examined the relationships of END to individual END models, including: A, infarct swelling; B, small subcortical infarct; C, mismatch; and D, recurrence. There were 163 patients recruited and 43 (26.4%) of them had END. The END models A, B and C significantly predicted END respectively after adjusting for confounding factors (p=0.022, p=0.007 and p<0.001 respectively). In END model D, we examined all imaging predictors of Recurrence Risk Estimator (RRE) individually and only the "multiple acute infarcts" pattern was significantly associated with END (p=0.032). When applying END models A, B, C and D, they successfully predicted END (p<0.001; odds ratio: 17.5[95% confidence interval: 5.1-60.8]), with 93.0% sensitivity, 60.0% specificity, 45.5% positive predictive value and 96.0% negative predictive value. The results demonstrate that the proposed model could predict END in all stroke subtypes of anterior circulation infarction. It provides a practical model for clinical physicians to select high-risk patients for more aggressive treatment to prevent END. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A European benchmarking system to evaluate in-hospital mortality rates in acute coronary syndrome: the EURHOBOP project.

PubMed

Dégano, Irene R; Subirana, Isaac; Torre, Marina; Grau, María; Vila, Joan; Fusco, Danilo; Kirchberger, Inge; Ferrières, Jean; Malmivaara, Antti; Azevedo, Ana; Meisinger, Christa; Bongard, Vanina; Farmakis, Dimitros; Davoli, Marina; Häkkinen, Unto; Araújo, Carla; Lekakis, John; Elosua, Roberto; Marrugat, Jaume

2015-03-01

Hospital performance models in acute myocardial infarction (AMI) are useful to assess patient management. While models are available for individual countries, mainly US, cross-European performance models are lacking. Thus, we aimed to develop a system to benchmark European hospitals in AMI and percutaneous coronary intervention (PCI), based on predicted in-hospital mortality. We used the EURopean HOspital Benchmarking by Outcomes in ACS Processes (EURHOBOP) cohort to develop the models, which included 11,631 AMI patients and 8276 acute coronary syndrome (ACS) patients who underwent PCI. Models were validated with a cohort of 55,955 European ACS patients. Multilevel logistic regression was used to predict in-hospital mortality in European hospitals for AMI and PCI. Administrative and clinical models were constructed with patient- and hospital-level covariates, as well as hospital- and country-based random effects. Internal cross-validation and external validation showed good discrimination at the patient level and good calibration at the hospital level, based on the C-index (0.736-0.819) and the concordance correlation coefficient (55.4%-80.3%). Mortality ratios (MRs) showed excellent concordance between administrative and clinical models (97.5% for AMI and 91.6% for PCI). Exclusion of transfers and hospital stays ≤1day did not affect in-hospital mortality prediction in sensitivity analyses, as shown by MR concordance (80.9%-85.4%). Models were used to develop a benchmarking system to compare in-hospital mortality rates of European hospitals with similar characteristics. The developed system, based on the EURHOBOP models, is a simple and reliable tool to compare in-hospital mortality rates between European hospitals in AMI and PCI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Histopathology of Septic Acute Kidney Injury: A Systematic Review of Experimental Data.

PubMed

Kosaka, Junko; Lankadeva, Yugeesh R; May, Clive N; Bellomo, Rinaldo

2016-09-01

The histopathologic changes associated with septic acute kidney injury are poorly understood, in part, because of the lack of biopsy data in humans. Animal models of septic acute kidney injury may help define such changes. Therefore, we performed a systematic review of the histopathologic changes found in modern experimental septic acute kidney injury models. MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and PubMed (from January 2007 to February 2015). We reviewed experimental studies reporting findings on the histopathology of contemporary experimental septic acute kidney injury. We focused on the presence or the absence of acute tubular necrosis, tubular cell apoptosis, and other nonspecific findings. We identified 102 studies in 1,059 animals. Among the 1,059 animals, 53 (5.0%) did not have any renal histopathologic changes, but acute tubular necrosis was found in 184 (17.4%). The prevalence of acute tubular necrosis was not related to animal size or model of sepsis and was only found in models with low cardiac output and decreased renal blood flow (p < 0.0001). Only 21 studies (170 animals) assessed the prevalence of tubular cell apoptosis, which was reported in 158 animals (92.9%). The prevalence of tubular cell apoptosis was significantly higher in studies using small animals (p < 0.0001) and in peritonitis models (p < 0.0001). Simultaneous acute tubular necrosis and tubular cell apoptosis was rare (55 animals [32.4%]) and only seen with decreased cardiac output and renal blood flow. Nonspecific changes (vacuolization of tubular cells, loss of brush border, and tubular cell swelling) were each observed in 423 (39.9%), 250 (23.6%) and 243 (22.9%) animals, respectively. In models of experimental septic acute kidney injury in contemporary articles, acute tubular necrosis was relatively uncommon and, when present, reflected the presence of an associated low cardiac output or low renal blood flow syndrome. Tubular cell apoptosis seemed frequent in the few studies in which it was investigated. Nonspecific morphologic changes, however, were the most common histopathologic findings.

Acute Effects of Exercise Mode on Arterial Stiffness and Wave Reflection in Healthy Young Adults: A Systematic Review and Meta-Analysis

PubMed Central

Pierce, Doris R.; Doma, Kenji; Leicht, Anthony S.

2018-01-01

Background: This systematic review and meta-analysis quantified the effect of acute exercise mode on arterial stiffness and wave reflection measures including carotid-femoral pulse wave velocity (cf-PWV), augmentation index (AIx), and heart rate corrected AIx (AIx75). Methods: Using standardized terms, database searches from inception until 2017 identified 45 studies. Eligible studies included acute aerobic and/or resistance exercise in healthy adults, pre- and post-intervention measurements or change values, and described their study design. Data from included studies were analyzed and reported in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA guidelines. Meta-analytical data were reported via forest plots using absolute differences with 95% confidence intervals with the random effects model accounting for between-study heterogeneity. Reporting bias was assessed via funnel plots and, individual studies were evaluated for bias using the Cochrane Collaboration's tool for assessing risk of bias. A modified PEDro Scale was applied to appraise methodological concerns inherent to included studies. Results: Acute aerobic exercise failed to change cf-PWV (mean difference: 0.00 ms−1 [95% confidence interval: −0.11, 0.11], p = 0.96), significantly reduced AIx (−4.54% [−7.05, −2.04], p = 0.0004) and significantly increased AIx75 (3.58% [0.56, 6.61], p = 0.02). Contrastingly, acute resistance exercise significantly increased cf-PWV (0.42 ms−1 [0.17, 0.66], p = 0.0008), did not change AIx (1.63% [−3.83, 7.09], p = 0.56), and significantly increased AIx75 (15.02% [8.71, 21.33], p < 0.00001). Significant heterogeneity was evident within all comparisons except cf-PWV following resistance exercise, and several methodological concerns including low applicability of exercise protocols and lack of control intervention were identified. Conclusions: Distinct arterial stiffness and wave reflection responses were identified following acute exercise with overall increases in both cf-PWV and AIx75 following resistance exercise potentially arising fromcardiovascular and non-cardiovascular factors that likely differ from those following aerobic exercise. Future studies should address identified methodological limitations to enhance interpretation and applicability of arterial stiffness and wave reflection indices to exercise and health. PMID:29487535

Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-κB activity

PubMed Central

Liu, Yong; Chen, Xiao-Dong; Yu, Jiang; Chi, Jun-Lin; Long, Fei-Wu; Yang, Hong-Wei; Chen, Ke-Ling; Lv, Zhao-Ying; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

2017-01-01

Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of l-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor-κB (NF-κB) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis. PMID:28300832

Characterization of acute and long-term pathologies of superficial and deep dermal sulfur mustard skin lesions in the hairless guinea pig model.

PubMed

Dachir, Shlomit; Cohen, Maayan; Kamus-Elimeleh, Dikla; Fishbine, Eliezer; Sahar, Rita; Gez, Rellie; Brandeis, Rachel; Horwitz, Vered; Kadar, Tamar

2012-01-01

Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measurements. Prostaglandin E(2) content, matrix metalloproteinase-2 and 9 activity, and histopathology were conducted up to 4 weeks post-exposure. Sulfur mustard skin injury, including erythema and edema, impairment of skin barrier and wounds developed in a dose-dependent manner. Prostaglandin E(2) content and matrix metalloproteinase-2 and 9 activities were elevated during the wound development and the healing process. Histological evaluation revealed severe damage to the epidermis and deep dermis and vesications. At 4 weeks postexposure, healing was not completed: significantly impaired stratum corneum, absence of hair follicles, and epidermal hyperplasia were observed. These results confirm the use of the superficial and deep dermal skin injuries in the hairless guinea pigs as suitable models that can be utilized for the investigation of the pathological processes of acute as well as long-term injuries. These models will be further used to develop treatments to improve the healing process and prevent skin damage and long-term effects. © 2012 by the Wound Healing Society.

Cost-effectiveness of the community-based management of severe acute malnutrition by community health workers in southern Bangladesh.

PubMed

Puett, Chloe; Sadler, Kate; Alderman, Harold; Coates, Jennifer; Fiedler, John L; Myatt, Mark

2013-07-01

This study assessed the cost-effectiveness of adding the community-based management of severe acute malnutrition (CMAM) to a community-based health and nutrition programme delivered by community health workers (CHWs) in southern Bangladesh. The cost-effectiveness of this model of treatment for severe acute malnutrition (SAM) was compared with the cost-effectiveness of the 'standard of care' for SAM (i.e. inpatient treatment), augmented with community surveillance by CHWs to detect cases, in a neighbouring area. An activity-based cost model was used, and a societal perspective taken, to include all costs incurred in the programme by providers and participants for the management of SAM in both areas. Cost data were coupled with programme effectiveness data. The community-based strategy cost US$26 per disability-adjusted life year (DALY) averted, compared with US$1344 per DALY averted for inpatient treatment. The average cost to participant households for their child to recover from SAM in community treatment was one-sixth that of inpatient treatment. These results suggest that this model of treatment for SAM is highly cost-effective and that CHWs, given adequate supervision and training, can be employed effectively to expand access to treatment for SAM in Bangladesh.

A concordance-based study to assess doctors’ and nurses’ mental models in Internal Medicine

PubMed Central

Chan, K. C. Gary; Muller-Juge, Virginie; Cullati, Stéphane; Hudelson, Patricia; Maître, Fabienne; Vu, Nu V.; Savoldelli, Georges L.; Nendaz, Mathieu R.

2017-01-01

Interprofessional collaboration between doctors and nurses is based on team mental models, in particular for each professional’s roles. Our objective was to identify factors influencing concordance on the expectations of doctors’ and nurses’ roles and responsibilities in an Internal Medicine ward. Using a dataset of 196 doctor-nurse pairs (14x14 = 196), we analyzed choices and prioritized management actions of 14 doctors and 14 nurses in six clinical nurse role scenarios, and in five doctor role scenarios (6 options per scenario). In logistic regression models with a non-nested correlation structure, we evaluated concordance among doctors and nurses, and adjusted for potential confounders (including prior experience in Internal Medicine, acuteness of case and gender). Concordance was associated with number of female professionals (adjusted OR 1.32, 95% CI 1.02 to 1.73), for acute situations (adjusted OR 2.02, 95% CI 1.13 to 3.62), and in doctor role scenarios (adjusted OR 2.19, 95% CI 1.32 to 3.65). Prior experience and country of training were not significant predictors of concordance. In conclusion, our concordance-based approach helped us identify areas of lower concordance in expected doctor-nurse roles and responsibilities, particularly in non-acute situations, which can be targeted by future interprofessional, educational interventions. PMID:28792524

Evaluation of the ecological relevance of mysid toxicity tests using population modeling techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuhn-Hines, A.; Munns, W.R. Jr.; Lussier, S.

1995-12-31

A number of acute and chronic bioassay statistics are used to evaluate the toxicity and risks of chemical stressors to the mysid shrimp, Mysidopsis bahia. These include LC{sub 50}S from acute tests, NOECs from 7-day and life-cycle tests, and the US EPA Water Quality Criteria Criterion Continuous Concentrations (CCC). Because these statistics are generated from endpoints which focus upon the responses of individual organisms, their relationships to significant effects at higher levels of ecological organization are unknown. This study was conducted to evaluate the quantitative relationships between toxicity test statistics and a concentration-based statistic derived from exposure-response models describing populationmore » growth rate ({lambda}) to stressor concentration. This statistic, C{sup {sm_bullet}} (concentration where {lambda} = I, zero population growth) describes the concentration above which mysid populations are projected to decline in abundance as determined using population modeling techniques. An analysis of M. bahia responses to 9 metals and 9 organic contaminants indicated the NOEC from life-cycle tests to be the best predictor of C{sup {sm_bullet}}, although the acute LC{sub 50} predicted population-level response surprisingly well. These analyses provide useful information regarding uncertainties of extrapolation among test statistics in assessments of ecological risk.« less

Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat

PubMed Central

Chen, Huaguo; Xu, Yongfu; Wang, Jianzhong; Zhao, Wei; Ruan, Huihui

2015-01-01

Baicalin belongs to glucuronic acid glycosides and after hydrolysisbaicalein and glucuronic acid come into being. It has such effects as clearing heat and removing toxicity, anti-inflammation, choleresis, bringing high blood pressure down, diuresis, anti-allergic reaction and so on. In this study, we investigated whether baicalin ameliorates isoproterenol-induced acute myocardial infarction and its mechanism. Rat model of acute myocardial infarction was induced by isoproterenol. Casein kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT) and infarct size measurement were used to measure the protective effect of baicalin on isoproterenol-induced acute myocardial infarction. iNOS protein expression in rat was analyzed using western blot analysis. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) and superoxide dismutase (SOD) and caspase-3 activation levels were explored using commercial ELISA kits. In the acute myocardial infarction experiment, baicalin effectively ameliorates the level of CK, CK-MB, LDH and cTnT, reduced infarct size in acute myocardial infarction rat model. Meanwhile, treatment with baicalin effectively decreased the iNOS protein expression, inflammatory factors and oxidative stresses in a rat model of acute myocardial infarction. However, baicalin emerged that anti-apoptosis activity and suppressed the activation of caspase-3 in a rat model of acute myocardial infarction. The data suggest that the protective effect of baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation and oxidative stress in rat. PMID:26617721

Acute exposure of mercury chloride stimulates the tissue regeneration program and reactive oxygen species production in the Drosophila midgut.

PubMed

Chen, Zhi; Wu, Xiaochun; Luo, Hongjie; Zhao, Lingling; Ji, Xin; Qiao, Xianfeng; Jin, Yaping; Liu, Wei

2016-01-01

We used Drosophila as an animal model to study the digestive tract in response to the exposure of inorganic mercury (HgCl2). We found that after oral administration, mercury was mainly sequestered within the midgut. This resulted in increased cell death, which in turn stimulated the tissue regeneration program, including accelerated proliferation and differentiation of the intestinal stem cells (ISCs). We further demonstrated that these injuries correlate closely with the excessive production of the reactive oxygen species (ROS), as vitamin E, an antioxidant reagent, efficiently suppressed the HgCl2-induced phenotypes of midgut and improved the viability. We propose that the Drosophila midgut could serve as a suitable model to study the treatment of acute hydrargyrism on the digestive systems. Copyright © 2015 Elsevier B.V. All rights reserved.

[Acute kidney injury after pediatric cardiac surgery: risk factors and outcomes. Proposal for a predictive model].

PubMed

Cardoso, Bárbara; Laranjo, Sérgio; Gomes, Inês; Freitas, Isabel; Trigo, Conceição; Fragata, Isabel; Fragata, José; Pinto, Fátima

2016-02-01

To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Histopathology and pathogenesis of caerulein-, duct ligation-, and arginine-induced acute pancreatitis in Sprague-Dawley rats and C57BL6 mice.

PubMed

Zhang, Jun; Rouse, Rodney L

2014-09-01

Three classical rodent models of acute pancreatitis were created in an effort to identify potential pre-clinical models of drug-induced pancreatitis (DIP) and candidate non-invasive biomarkers for improved detection of DIP. Study objectives included designing a lexicon to minimize bias by capturing normal variation and spontaneous and injury-induced changes while maintaining the ability to statistically differentiate degrees of change, defining morphologic anchors for novel pancreatic injury biomarkers, and improved understanding of mechanisms responsible for pancreatitis. Models were created in male Sprague-Dawley rats and C57BL6 mice through: 1) administration of the cholecystokinin analog, caerulein; 2) administration of arginine; 3) surgical ligation of the pancreatic duct. Nine morphologically detectable processes were used in the lexicon; acinar cell hypertrophy; acinar cell autophagy; acinar cell apoptosis; acinar cell necrosis; vascular injury; interstitial edema, inflammation and hemorrhage; fat necrosis; ductal changes; acinar cell atrophy. Criteria were defined for scoring levels (0 = absent, 1 = mild, 2 = moderate, 3 = severe) for each lexicon component. Consistent with previous studies, histopathology scores were significant greater in rats compared to mice at baseline and after treatment. The histopathology scores in caerulein and ligation-treated rats and mice were significantly greater than those of arginine-treated rats and mice. The present study supports a multifaceted pathogenesis for acute pancreatitis in which intra-acinar trypsinogen activation, damage to acinar cells, fat cells, and vascular cells as well as activation/degranulation of mast cells and activated macrophages all contribute to the initiation and/or progression of acute inflammation of the exocrine pancreas.

Role of Interleukin-10 in Acute Brain Injuries

PubMed Central

Garcia, Joshua M.; Stillings, Stephanie A.; Leclerc, Jenna L.; Phillips, Harrison; Edwards, Nancy J.; Robicsek, Steven A.; Hoh, Brian L.; Blackburn, Spiros; Doré, Sylvain

2017-01-01

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine expressed in response to brain injury, where it facilitates the resolution of inflammatory cascades, which if prolonged causes secondary brain damage. Here, we comprehensively review the current knowledge regarding the role of IL-10 in modulating outcomes following acute brain injury, including traumatic brain injury (TBI) and the various stroke subtypes. The vascular endothelium is closely tied to the pathophysiology of these neurological disorders and research has demonstrated clear vascular endothelial protective properties for IL-10. In vitro and in vivo models of ischemic stroke have convincingly directly and indirectly shown IL-10-mediated neuroprotection; although clinically, the role of IL-10 in predicting risk and outcomes is less clear. Comparatively, conclusive studies investigating the contribution of IL-10 in subarachnoid hemorrhage are lacking. Weak indirect evidence supporting the protective role of IL-10 in preclinical models of intracerebral hemorrhage exists; however, in the limited number of clinical studies, higher IL-10 levels seen post-ictus have been associated with worse outcomes. Similarly, preclinical TBI models have suggested a neuroprotective role for IL-10; although, controversy exists among the several clinical studies. In summary, while IL-10 is consistently elevated following acute brain injury, the effect of IL-10 appears to be pathology dependent, and preclinical and clinical studies often paradoxically yield opposite results. The pronounced and potent effects of IL-10 in the resolution of inflammation and inconsistency in the literature regarding the contribution of IL-10 in the setting of acute brain injury warrant further rigorously controlled and targeted investigation. PMID:28659854

META-ANALYSIS OF ACUTE EXERCISE EFFECTS ON STATE ANXIETY: AN UPDATE OF RANDOMIZED CONTROLLED TRIALS OVER THE PAST 25 YEARS.

PubMed

Ensari, Ipek; Greenlee, Tina A; Motl, Robert W; Petruzzello, Steven J

2015-08-01

One prominent and well-cited meta-analysis published nearly 25 years ago reported that an acute or single bout of exercise reduced state anxiety by approximately ¼ standard deviation. We conducted a meta-analysis of randomized controlled trials (RCTs) published after that meta-analysis for updating our understanding of the acute effects of exercise on state anxiety. We searched PubMed, EBSCOHost, Medline, PsycINFO, ERIC, and ScienceDirect for RCTs of acute exercise and state anxiety as an outcome. There were 36 RCTs that met inclusion criteria and yielded data for effect size (ES) generation (Cohen's d). An overall ES was calculated using a random effects model and expressed as Hedge's g. The weighted mean ES was small (Hedge's g = 0.16, standard error (SE) = 0.06), but statistically significant (P < 0.05), and indicated that a single bout of exercise resulted in an improvement in state anxiety compared with control. The overall ES was heterogeneous and post hoc, exploratory analyses using both random- and fixed-effects models identified several variables as moderators including sample age, sex and health status, baseline activity levels, exercise intensity, modality and control condition, randomization, overall study quality, and the anxiety measure (P < 0.05). The cumulative evidence from high quality studies indicates that acute bouts of exercise can yield a small reduction in state anxiety. The research is still plagued by floor effects associated with recruiting persons with normal or lower levels of state anxiety, and this should be overcome in subsequent trials. © 2015 Wiley Periodicals, Inc.

Acute Surgical Unit: a new model of care.

PubMed

Cox, Michael R; Cook, Lyn; Dobson, Jennifer; Lambrakis, Paul; Ganesh, Shanthan; Cregan, Patrick

2010-06-01

The traditional on-call system for the management of acute general surgical admissions is inefficient and outdated. A new model, Acute Surgical Unit (ASU), was developed at Nepean Hospital in 2006. The ASU is a consultant-driven, independent unit that manages all acute general surgical admissions. The team has the same make up 7 days a week and functions the same every day, including weekends and public holidays. The consultant does a 24-h period of on-call, from 7 pm to 7 pm. They are on remote call from 7 pm to 7 am and are in the hospital from 7 am to 7 pm with their sole responsibility being to the ASU. The ASU has a day team with two registrars, two residents and a nurse practitioner. All patients are admitted and stay in the ASU until discharge or transfer to other units. Handover of the patients at the end of each day is facilitated by a comprehensive ASU database. The implementation of the ASU at Nepean Hospital has improved the timing of assessment by the surgical unit. There has been significant improvement in the timing of operative management, with an increased number and proportion of cases being done during daylight hours, with an associated reduction in the proportion of cases performed afterhours. There is greater trainee supervision with regard to patient assessment, management and operative procedures. There has been an improvement in the consultants' work conditions. The ASU provides an excellent training opportunity for surgical trainees, residents and interns in the assessment and management of acute surgical conditions.

Potential Application of Viral Empty Capsids for the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

DTIC Science & Technology

2016-07-01

Particles (VLPs). The rationale is based on the beneficial effect of SV40 VLPs on an Acute Kidney Injury (AKI) model in mice, previously demonstrated...signaling which, as was demonstrated, protect mice kidneys from apoptosis, necrosis and consequent damage induced by a toxic (mercury) insult, increasing...recombinant VP1, without any genetic material. Using a mouse model for toxic Acute Kidney Injury (AKI), we demonstrated that systemic

Development of an acute oral toxicity dataset to facilitate assessment of existing QSARs and development of new models (WC10)

EPA Science Inventory

Acute oral toxicity data are used to meet both regulatory and non-regulatory needs. Recently, there have been efforts to explore alternative approaches for predicting acute oral toxicity such as QSARs. Evaluating the performance and scope of existing models and investigating the ...

Pharmacological interventions for acute pancreatitis.

PubMed

Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-21

In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. To assess the effects of different pharmacological interventions in people with acute pancreatitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials. seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life. Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).

Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia

PubMed Central

Ramsey, Laura B.; Janke, Laura J.; Payton, Monique A.; Cai, Xiangjun; Paugh, Steven W.; Karol, Seth E.; Kamdem, Landry Kamdem; Cheng, Cheng; Williams, Richard T.; Jeha, Sima; Pui, Ching-Hon; Evans, William E.; Relling, Mary V.

2015-01-01

Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples) or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM) were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model) we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002). Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia. PMID:26252865

Acute Brain Dysfunction: Development and Validation of a Daily Prediction Model.

PubMed

Marra, Annachiara; Pandharipande, Pratik P; Shotwell, Matthew S; Chandrasekhar, Rameela; Girard, Timothy D; Shintani, Ayumi K; Peelen, Linda M; Moons, Karl G M; Dittus, Robert S; Ely, E Wesley; Vasilevskis, Eduard E

2018-03-24

The goal of this study was to develop and validate a dynamic risk model to predict daily changes in acute brain dysfunction (ie, delirium and coma), discharge, and mortality in ICU patients. Using data from a multicenter prospective ICU cohort, a daily acute brain dysfunction-prediction model (ABD-pm) was developed by using multinomial logistic regression that estimated 15 transition probabilities (from one of three brain function states [normal, delirious, or comatose] to one of five possible outcomes [normal, delirious, comatose, ICU discharge, or died]) using baseline and daily risk factors. Model discrimination was assessed by using predictive characteristics such as negative predictive value (NPV). Calibration was assessed by plotting empirical vs model-estimated probabilities. Internal validation was performed by using a bootstrap procedure. Data were analyzed from 810 patients (6,711 daily transitions). The ABD-pm included individual risk factors: mental status, age, preexisting cognitive impairment, baseline and daily severity of illness, and daily administration of sedatives. The model yielded very high NPVs for "next day" delirium (NPV: 0.823), coma (NPV: 0.892), normal cognitive state (NPV: 0.875), ICU discharge (NPV: 0.905), and mortality (NPV: 0.981). The model demonstrated outstanding calibration when predicting the total number of patients expected to be in any given state across predicted risk. We developed and internally validated a dynamic risk model that predicts the daily risk for one of three cognitive states, ICU discharge, or mortality. The ABD-pm may be useful for predicting the proportion of patients for each outcome state across entire ICU populations to guide quality, safety, and care delivery activities. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Contrasting dynamic responses in vivo of the Bcl-xL and Bim erythropoietic survival pathways

PubMed Central

Koulnis, Miroslav; Porpiglia, Ermelinda; Porpiglia, P. Alberto; Liu, Ying; Hallstrom, Kelly; Hidalgo, Daniel

2012-01-01

Survival signaling by the erythropoietin (Epo) receptor (EpoR) is essential for erythropoiesis and for its acceleration in hypoxic stress. Several apparently redundant EpoR survival pathways were identified in vitro, raising the possibility of their functional specialization in vivo. Here we used mouse models of acute and chronic stress, including a hypoxic environment and β-thalassemia, to identify two markedly different response dynamics for two erythroblast survival pathways in vivo. Induction of the antiapoptotic protein Bcl-xL is rapid but transient, while suppression of the proapoptotic protein Bim is slower but persistent. Similar to sensory adaptation, however, the Bcl-xL pathway “resets,” allowing it to respond afresh to acute stress superimposed on a chronic stress stimulus. Using “knock-in” mouse models expressing mutant EpoRs, we found that adaptation in the Bcl-xL response occurs because of adaptation of its upstream regulator Stat5, both requiring the EpoR distal cytoplasmic domain. We conclude that survival pathways show previously unsuspected functional specialization for the acute and chronic phases of the stress response. Bcl-xL induction provides a “stop-gap” in acute stress, until slower but permanent pathways are activated. Furthermore, pathologic elevation of Bcl-xL may be the result of impaired adaptation, with implications for myeloproliferative disease mechanisms. PMID:22086418

Exploring the role of experiential avoidance from the perspective of attachment theory and the dual process model.

PubMed

Shear, M Katherine

2010-01-01

Avoidance can be adaptive and facilitate the healing process of acute grief or it can be maladaptive and hinder this same process. Maladaptive cognitive or behavioral avoidance comprises the central feature of the condition of complicated grief. This article explores the concept of experiential avoidance as it applies to bereavement, including when it is adaptive when it is problematic. Adaptive avoidance is framed using an attachment theory perspective and incorporates insights from the dual process model (DPM). An approach to clinical management of experiential avoidance in the syndrome of complicated grief is included.

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity

PubMed Central

Neville, Andrew J.; Zach, Sydney J.; Wang, Xiaofang; Larson, Joshua J.; Judge, Abigail K.; Davis, Lisa A.; Vennerstrom, Jonathan L.

2015-01-01

Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available drugs that have shown efficacy in disease models but which lack clinical case reports. Ideally, less-toxic treatments for the acute disease can be identified and developed, with an additional goal of cyst clearance from human and animal hosts. PMID:26392504

Modeling the adenosine system as a modulator of cognitive performance and sleep patterns during sleep restriction and recovery.

PubMed

Phillips, Andrew J K; Klerman, Elizabeth B; Butler, James P

2017-10-01

Sleep loss causes profound cognitive impairments and increases the concentrations of adenosine and adenosine A1 receptors in specific regions of the brain. Time courses for performance impairment and recovery differ between acute and chronic sleep loss, but the physiological basis for these time courses is unknown. Adenosine has been implicated in pathways that generate sleepiness and cognitive impairments, but existing mathematical models of sleep and cognitive performance do not explicitly include adenosine. Here, we developed a novel receptor-ligand model of the adenosine system to test the hypothesis that changes in both adenosine and A1 receptor concentrations can capture changes in cognitive performance during acute sleep deprivation (one prolonged wake episode), chronic sleep restriction (multiple nights with insufficient sleep), and subsequent recovery. Parameter values were estimated using biochemical data and reaction time performance on the psychomotor vigilance test (PVT). The model closely fit group-average PVT data during acute sleep deprivation, chronic sleep restriction, and recovery. We tested the model's ability to reproduce timing and duration of sleep in a separate experiment where individuals were permitted to sleep for up to 14 hours per day for 28 days. The model accurately reproduced these data, and also correctly predicted the possible emergence of a split sleep pattern (two distinct sleep episodes) under these experimental conditions. Our findings provide a physiologically plausible explanation for observed changes in cognitive performance and sleep during sleep loss and recovery, as well as a new approach for predicting sleep and cognitive performance under planned schedules.

Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice.

PubMed

Koh, Seong-Joon; Choi, Youn-I; Kim, Yuri; Kim, Yoo-Sun; Choi, Sang Woon; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae

2018-05-09

Walnuts (Juglans regia) are known to have anti-cancer and immunomodulatory effects. However, little information is available on the effects of walnut phenolic extract (WPE) on intestinal inflammation and colitis-associated colon cancer. COLO205 cells were pretreated with WPE and then stimulated with tumor necrosis factor (TNF)-α. In the acute colitis model, wild type mice (C57BL/6) were administered 4% dextran sulfate sodium (DSS) for 5 days. In the chronic colitis model, interleukin (IL)-10 -/- mice were administered with either the vehicle or WPE (20 mg/kg) by oral gavage daily for 2 weeks. In an inflammation-associated tumor model, wild type mice were administered a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. WPE significantly inhibited IL-8 and IL-1α expression in COLO205 cells. WPE attenuated both the TNF-α-induced IκB phosphorylation/degradation and NF-κB DNA binding activity. The administration of oral WPE significantly reduced the severity of colitis in both acute and chronic colitis models, including the IL-10 -/- mice. In immunohistochemical staining, WPE attenuated NF-κB signaling in the colons of both colitis models. Finally, WPE also significantly reduced tumor development in a murine model of colitis-associated colon cancer (CAC). WPE ameliorates acute and chronic colitis and CAC in mice, suggesting that WPE may have potentials for the treatment of inflammatory bowel disease.

An inducible model of abacterial prostatitis induces antigen specific inflammatory and proliferative changes in the murine prostate

PubMed Central

Haverkamp, Jessica M.; Charbonneau, Bridget; Meyerholz, David K.; Cohen, Michael B.; Snyder, Paul W.; Svensson, Robert U.; Henry, Michael D.; Wang, Hsing- Hui

2011-01-01

Background Prostatitis is a poorly understood disease and increasing evidence suggests inflammation is involved in other prostatic diseases, including prostate cancer. Methods The ability of pre-activated CD8 T cells to induce prostatitis was examined by adoptive transfer into POET-3 mice or POET-3/Luc/Pten−/+ mice. Characterization of the inflammatory response was determined by examining leukocyte infiltration by histological analysis, flow cytometry and by evaluating cytokine and chemokine levels in prostate tissue. The impact of inflammation on the prostate was evaluated by monitoring epithelial cell proliferation over time. Results Initiation of inflammation by ovalbumin specific CD8+ T cells (OT-I cells) resulted in development of acute prostatitis in the anterior, dorsolateral and anterior prostate of POET-3 and POET-3/Luc/Pten−/+ mice. Acute prostatitis was characterized by recruitment of adoptively transferred OT-I cells and importantly, autologous CD4+ and CD8+ T cells, myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg). In concert with leukocyte infiltration elevated levels of pro-inflammatory cytokines and chemokines were observed. Inflammation also resulted in marked epithelial cell proliferation that was sustained up to 80 days post adoptive-transfer of OT-I cells. Conclusions The POET-3 model represents a novel mouse model to study both acute and chronic prostate inflammation in an antigen-specific system. Further, the POET-3 mouse model can be crossed with other genetic models of disease such as the C57/Luc/Pten−/− model of prostate cancer, allowing the impact of prostatitis on other prostatic diseases to be evaluated. PMID:21656824

Effectiveness of team nursing compared with total patient care on staff wellbeing when organizing nursing work in acute care wards: a systematic review.

PubMed

King, Allana; Long, Lesley; Lisy, Karolina

2015-11-01

The organization of the work of nurses, according to recognized models of care, can have a significant impact on the wellbeing and performance of nurses and nursing teams. This review focuses on two models of nursing care delivery, namely, team and total patient care, and their effect on nurses' wellbeing. To examine the effectiveness of team nursing compared to total patient care on staff wellbeing when organizing nursing work in acute care wards. Participants were nurses working on wards in acute care hospitals.The intervention was the use of a team nursing model when organizing nursing work. The comparator was the use of a total patient care model.This review considered quantitative study designs for inclusion in the review.The outcome of interest was staff wellbeing which was measured by staff outcomes in relation to job satisfaction, turnover, absenteeism, stress levels and burnout. The search strategy aimed to find both published and unpublished studies from 1995 to April 21, 2014. Quantitative papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute. Data was extracted from papers included in the review using the standardized data extraction tool from the Joanna Briggs Institute. The data extracted included specific details about the interventions, populations, study methods and outcomes of significance to the review question and its specific objectives. Due to the heterogeneity of the included quantitative studies, meta-analysis was not possible. Results have been presented in a narrative form. The database search returned 10,067 records. Forty-three full text titles were assessed, and of these 40 were excluded, resulting in three studies being included in the review. Two of the studies were quasi experimental designs and the other was considered an uncontrolled before and after experimental study. There were no statistically significant differences observed in any study in the overall job satisfaction of nurses using a team nursing model compared with a total patient care model. Some differences in job satisfaction were however observed within different subgroups of nurses. There were no statistically significant differences in either stress or job tension. Within the selected studies, the specific outcomes of absenteeism and burnout were not addressed. Due to the limited number of quantitative studies identified for inclusion in this systematic review it is not possible to determine whether organizing nursing work in a team nursing or total patient care model is more effective in terms of staff wellbeing in acute care settings. Neither a team nursing or total patient care model had a significant influence on nurses' overall job satisfaction, stress levels or staff turnover. This review could not ascertain if the type of model of care affects absenteeism or burnout as these were not addressed in any of the identified studies.Caution should be taken when evaluating which model of care is appropriate and the decision needs to incorporate staff experience levels and staff skill mix. There needs to be clear definition of nursing roles.This review demonstrates the need for further quantitative studies of these models of care that are well designed with sufficient sample sizes to allow for attrition of participants, and that explore the impact each model has on nurse's wellbeing, in particular, studies that address burnout and absenteeism. There is a need for consistent terminology to allow for future comparison and research to occur at an international level. Future studies on models of care should include economic analysis to fully inform policy and practice.

Prediction of acute respiratory disease in current and former smokers with and without COPD.

PubMed

Bowler, Russell P; Kim, Victor; Regan, Elizabeth; Williams, André A A; Santorico, Stephanie A; Make, Barry J; Lynch, David A; Hokanson, John E; Washko, George R; Bercz, Peter; Soler, Xavier; Marchetti, Nathaniel; Criner, Gerard J; Ramsdell, Joe; Han, MeiLan K; Demeo, Dawn; Anzueto, Antonio; Comellas, Alejandro; Crapo, James D; Dransfield, Mark; Wells, J Michael; Hersh, Craig P; MacIntyre, Neil; Martinez, Fernando; Nath, Hrudaya P; Niewoehner, Dennis; Sciurba, Frank; Sharafkhaneh, Amir; Silverman, Edwin K; van Beek, Edwin J R; Wilson, Carla; Wendt, Christine; Wise, Robert A

2014-10-01

The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George's Respiratory Questionnaire score). Risks were similar for those with and without COPD. Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD.

Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD

PubMed Central

Kim, Victor; Regan, Elizabeth; Williams, André A. A.; Santorico, Stephanie A.; Make, Barry J.; Lynch, David A.; Hokanson, John E.; Washko, George R.; Bercz, Peter; Soler, Xavier; Marchetti, Nathaniel; Criner, Gerard J.; Ramsdell, Joe; Han, MeiLan K.; Demeo, Dawn; Anzueto, Antonio; Comellas, Alejandro; Crapo, James D.; Dransfield, Mark; Wells, J. Michael; Hersh, Craig P.; MacIntyre, Neil; Martinez, Fernando; Nath, Hrudaya P.; Niewoehner, Dennis; Sciurba, Frank; Sharafkhaneh, Amir; Silverman, Edwin K.; van Beek, Edwin J. R.; Wilson, Carla; Wendt, Christine; Wise, Robert A.; Curtis, Jeffrey; Kazerooni, Ella; Hanania, Nicola; Alapat, Philip; Bandi, Venkata; Guntupalli, Kalpalatha; Guy, Elizabeth; Lunn, William; Mallampalli, Antara; Trinh, Charles; Atik, Mustafa; DeMeo, Dawn; Hersh, Craig; Jacobson, Francine; Graham Barr, R.; Thomashow, Byron; Austin, John; MacIntyre, Neil; Washington, Lacey; Page McAdams, H.; Rosiello, Richard; Bresnahan, Timothy; McEvoy, Charlene; Tashjian, Joseph; Wise, Robert; Hansel, Nadia; Brown, Robert; Casaburi, Richard; Porszasz, Janos; Fischer, Hans; Budoff, Matt; Sharafkhaneh, Amir; Niewoehner, Dennis; Allen, Tadashi; Rice, Kathryn; Foreman, Marilyn; Westney, Gloria; Berkowitz, Eugene; Bowler, Russell; Friedlander, Adam; Meoni, Eleonora; Criner, Gerard; Kim, Victor; Marchetti, Nathaniel; Satti, Aditi; James Mamary, A.; Steiner, Robert; Dass, Chandra; Bailey, William; Dransfield, Mark; Gerald, Lynn; Nath, Hrudaya; Ramsdell, Joe; Ferguson, Paul; Friedman, Paul; McLennan, Geoffrey; van Beek, Edwin JR; Martinez, Fernando; Han, MeiLan; Thompson, Deborah; Kazerooni, Ella; Wendt, Christine; Allen, Tadashi; Sciurba, Frank; Weissfeld, Joel; Fuhrman, Carl; Bon, Jessica; Anzueto, Antonio; Adams, Sandra; Orozco, Carlos; Santiago Restrepo, C.; Mumbower, Amy; Crapo, James; Silverman, Edwin; Make, Barry; Regan, Elizabeth; Samet, Jonathan; Willis, Amy; Stinson, Douglas; Beaty, Terri; Klanderman, Barbara; Laird, Nan; Lange, Christoph; Ionita, Iuliana; Santorico, Stephanie; Silverman, Edwin; Lynch, David; Schroeder, Joyce; Newell, John; Reilly, John; Coxson, Harvey; Judy, Philip; Hoffman, Eric; San Jose Estepar, Raul; Washko, George; Leek, Rebecca; Zach, Jordan; Kluiber, Alex; Rodionova, Anastasia; Mann, Tanya; Crapo, Robert; Jensen, Robert; Farzadegan, Homayoon; Murphy, James; Everett, Douglas; Wilson, Carla; Hokanson, John

2014-01-01

BACKGROUND: The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS: Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS: At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George’s Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS: Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD. PMID:24945159

Genetics Home Reference: porphyria

MedlinePlus

... control breathing become paralyzed. Acute porphyrias include acute intermittent porphyria and ALAD deficiency porphyria . Two other forms ... the disease never experience signs or symptoms. Acute intermittent porphyria is the most common form of acute ...

The experience of acute leukaemia in adult patients: a qualitative thematic synthesis.

PubMed

Papadopoulou, Constantina; Johnston, Bridget; Themessl-Huber, Markus

2013-10-01

The aim of this review was to systematically identify and synthesise all qualitative evidence on how adult patients diagnosed with acute leukaemia experience living with their illness. A systematic search strategy was developed comprising of two search strings: i) acute leukaemia and ii) qualitative methodology. The search strategy was run in seven electronic databases (Medline, CINAHL, PsychINFO, EMBASE, BNI & Archive, SSCI and ASSIA). Nine qualitative studies in adult patients with acute leukaemia, published in peer reviewed journals between 01/1990 and 01/2013 were included in the final sample. The qualitative thematic synthesis resulted in the development of a conceptual model describing a person's path to build a renewed self. Following the initial blow of diagnosis with the range of initial reactions, patients with acute leukaemia are living in a contracting world; they have to deal with the life in hospital, the several losses and the impact of their illness on their emotions and interpersonal relationships. Several factors take up a buffering role at that stage: coping, support, information and hope. Finally, patients accommodate acute leukaemia in their lives through re-evaluating personal values and assigning new meaning to their experience. Results from this thematic synthesis are indicative of the impact of acute leukaemia on patients' lives and the processes they use to make sense and accommodate the illness in their life. Increasing our understanding of these processes is warranted to improve patient care. Copyright © 2013. Published by Elsevier Ltd.

Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola virus in Rhesus Monkeys

DTIC Science & Technology

2016-03-02

distribution to sanctuary sites for viral 46 replication including testes, eye , and brain. In a rhesus monkey model of EVD, once daily 47...including respiratory syncytial virus (RSV), Junin virus (JUNV), Lassa fever virus 121 (LASV) and Middle East respiratory syndrome virus (MERS), with...yellow fever virus, dengue virus type 2), parainfluenza type 3, and severe 124 acute respiratory syndrome (SARS) associated coronavirus but little or

Current issues in Scandinavian acute psychiatric wards.

PubMed

Ruud, Torleif; Lindefors, Nils; Lindhardt, Anne

2006-01-01

The aim of the paper is to provide an overview of some of the most important issues faced by acute inpatient facilities in three Scandinavian countries, including reflections and critical remarks for discussion in this field. Information was drawn from scientific articles and official reports published in recent years, as well as the authors' own knowledge of acute facilities in their home countries. Acute inpatient facilities, including General Hospital Psychiatric Units (GHPUs), in all Scandinavian countries have several issues and problems in common, which include the organisation and capacity of acute services, the assessment of dangerousness and suicidality, the use of coercion and efforts to reduce coercion, the need to define and improve the quality of acute services, and the necessity to improve collaboration and continuity between acute services and other services. Although the emphasis some of these issues receive can vary across the three countries, Scandinavian mental health professionals (and policy makers) have begun to systematically share their experiences in developing a growing spirit of collaboration. Despite the role of welfare state and the deployment of substantial resources in Scandinavian countries, mental health practitioners are struggling to implement best practices in acute wards, to develop differentiated forms of acute services, and to reach the right balance and coordination between acute services and other services.

Serum Uric Acid Is Associated with Poor Outcome in Black Africans in the Acute Phase of Stroke

PubMed Central

Ayeah, Chia Mark; Ba, H.; Mbahe, Salomon

2017-01-01

Background Prognostic significance of serum uric acid (SUA) in acute stroke still remains controversial. Objectives To determine the prevalence of hyperuricemia and its association with outcome of stroke patients in the Douala General Hospital (DGH). Methods This was a hospital based prospective cohort study which included acute stroke patients with baseline SUA levels and 3-month poststroke follow-up data. Associations between high SUA levels and stroke outcomes were analyzed using multiple logistic regression and survival analysis (Cox regression and Kaplan-Meier). Results A total of 701 acute stroke patients were included and the prevalence of hyperuricemia was 46.6% with a mean SUA level of 68.625 ± 24 mg/l. Elevated SUA after stroke was associated with death (OR = 2.067; 95% CI: 1.449–2.950; p < 0.001) but did not predict this issue. However, an independent association between increasing SUA concentration and mortality was noted in a Cox proportional hazards regression model (adjusted HR = 1.740; 95% CI: 1.305–2.320; p < 0.001). Furthermore, hyperuricemia was an independent predictor of poor functional outcome within 3 months after stroke (OR = 2.482; 95% CI: 1.399–4.404; p = 0.002). Conclusion The prevalence of hyperuricemia in black African stroke patients is quite high and still remains a predictor of poor outcome. PMID:29082062

Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

PubMed

Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

2016-09-01

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

Long-Term Follow-up of the Delayed Effects of Acute Radiation Exposure in Primates

DTIC Science & Technology

2016-10-01

MV, Katz BP, Smith CP, Jackson W 3rd, Cohen DM, et al. A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management...subsyndrome of the acute radiation syndrome : a rhesus macaque model. Health Phys 2012; 103:411–26. 32. Robbins ME, Bourland JD, Cline JM, Wheeler KT, Deadwyler...AD______________ AWARD NUMBER: W81XWH-15-1-0574 TITLE: Long-Term Follow-up of the Delayed Effects of Acute Radiation Exposure in Primates

A metabolomics and mouse models approach to study inflammatory and immune responses to radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fornace, Albert J.; Li, Henghong

2013-12-02

The three-year project entitled "A Metabolomics and Mouse Models Approach to Study Inflammatory and Immune Responses to Radiation" was initiated in September 2009. The overall objectives of this project were to investigate the acute and persistent effects of low dose radiation on T cell lymphocyte function and physiology, as well the contributions of these cells to radiation-induced inflammatory responses. Inflammation after ionizing radiation (IR), even at low doses, may impact a variety of disease processes, including infectious disease, cardiovascular disease, cancer, and other potentially inflammatory disorders. There were three overall specific aims: 1. To investigate acute and persistent effects ofmore » low dose radiation on T cell subsets and function; 2. A genetic approach with mouse models to investigate p38 MAPK pathways that are involved in radiation-induced inflammatory signaling; 3. To investigate the effect of radiation quality on the inflammatory response. We have completed the work proposed in these aims.« less

The evolution of Drosophila melanogaster as a model for alcohol research.

PubMed

Devineni, Anita V; Heberlein, Ulrike

2013-07-08

Animal models have been widely used to gain insight into the mechanisms underlying the acute and long-term effects of alcohol exposure. The fruit fly Drosophila melanogaster encounters ethanol in its natural habitat and possesses many adaptations that allow it to survive and thrive in ethanol-rich environments. Several assays to study ethanol-related behaviors in flies, ranging from acute intoxication to self-administration and reward, have been developed in the past 20 years. These assays have provided the basis for studying the physiological and behavioral effects of ethanol and for identifying genes mediating these effects. In this review we describe the ecological relationship between flies and ethanol, the effects of ethanol on fly development and behavior, the use of flies as a model for alcohol addiction, and the interaction between ethanol and social behavior. We discuss these advances in the context of their utility to help decipher the mechanisms underlying the diverse effects of ethanol, including those that mediate ethanol dependence and addiction in humans.

A model for emergency department end-of-life communications after acute devastating events--part I: decision-making capacity, surrogates, and advance directives.

PubMed

Limehouse, Walter E; Feeser, V Ramana; Bookman, Kelly J; Derse, Arthur

2012-09-01

Making decisions for a patient affected by sudden devastating illness or injury traumatizes a patient's family and loved ones. Even in the absence of an emergency, surrogates making end-of-life treatment decisions may experience negative emotional effects. Helping surrogates with these end-of-life decisions under emergent conditions requires the emergency physician (EP) to be clear, making medical recommendations with sensitivity. This model for emergency department (ED) end-of-life communications after acute devastating events comprises the following steps: 1) determine the patient's decision-making capacity; 2) identify the legal surrogate; 3) elicit patient values as expressed in completed advance directives; 4) determine patient/surrogate understanding of the life-limiting event and expectant treatment goals; 5) convey physician understanding of the event, including prognosis, treatment options, and recommendation; 6) share decisions regarding withdrawing or withholding of resuscitative efforts, using available resources and considering options for organ donation; and 7) revise treatment goals as needed. Emergency physicians should break bad news compassionately, yet sufficiently, so that surrogate and family understand both the gravity of the situation and the lack of long-term benefit of continued life-sustaining interventions. EPs should also help the surrogate and family understand that palliative care addresses comfort needs of the patient including adequate treatment for pain, dyspnea, or anxiety. Part I of this communications model reviews determination of decision-making capacity, surrogacy laws, and advance directives, including legal definitions and application of these steps; Part II (which will appear in a future issue of AEM) covers communication moving from resuscitative to end-of-life and palliative treatment. EPs should recognize acute devastating illness or injuries, when appropriate, as opportunities to initiate end-of-life discussions and to implement shared decisions. © 2012 by the Society for Academic Emergency Medicine.

HLA-B27 Anterior Uveitis: Immunology and Immunopathology.

PubMed

Wakefield, Denis; Yates, William; Amjadi, Shahriar; McCluskey, Peter

2016-08-01

Acute anterior uveitis (AAU) is the commonest type of uveitis and HLA-B27 AAU is the most frequently recognized type of acute anterior uveitis and anterior uveitis overall. Recent evidence indicates that acute anterior uveitis is a heterogenous disease, is polygenic and is frequently associated with the spondyloarthropathies (SpA). Studies of patients with AAU and animal models of disease indicate a role for innate immunity, the IL-23 cytokine pathway and exogenous factors, in the pathogenesis of both SpA and acute anterior uveitis. Recently described genetic associations cluster around immunologic pathways, including the IL-17 and IL-23 pathways, antigen processing and presentation, and lymphocyte development and activation. Patients with ankylosing spondylitis (AS) and AAU share other genetic markers, such as ERAP-1, which show strong evidence of gene-gene interaction and point to new mechanisms of disease pathogenesis. These observations have major implications for understanding the pathogenesis of HLA-B27 diseases, such as AAU, and may lead to the development of more specific therapy for AAU. Received 6 January 2016; revised 6 February 2016; accepted 18 February 2016; published online 31 May 2016.

Predictors of the development of myocarditis or acute renal failure in patients with leptospirosis: An observational study

PubMed Central

2012-01-01

Background Leptospirosis has a varied clinical presentation with complications like myocarditis and acute renal failure. There are many predictors of severity and mortality including clinical and laboratory parameters. Early detection and treatment can reduce complications. Therefore recognizing the early predictors of the complications of leptospirosis is important in patient management. This study was aimed at determining the clinical and laboratory predictors of myocarditis or acute renal failure. Methods This was a prospective descriptive study carried out in the Teaching Hospital, Kandy, from 1st July 2007 to 31st July 2008. Patients with clinical features compatible with leptospirosis case definition were confirmed using the Microscopic Agglutination Test (MAT). Clinical features and laboratory measures done on admission were recorded. Patients were observed for the development of acute renal failure or myocarditis. Chi-square statistics, Fisher's exact test and Mann-Whitney U test were used to compare patients with and without complications. A logistic regression model was used to select final predictor variables. Results Sixty two confirmed leptospirosis patients were included in the study. Seven patients (11.3%) developed acute renal failure and five (8.1%) developed myocarditis while three (4.8%) had both acute renal failure and myocarditis. Conjunctival suffusion - 40 (64.5%), muscle tenderness - 28 (45.1%), oliguria - 20 (32.2%), jaundice - 12 (19.3%), hepatomegaly - 10 (16.1%), arrhythmias (irregular radial pulse) - 8 (12.9%), chest pain - 6 (9.7%), bleeding - 5 (8.1%), and shortness of breath (SOB) 4 (6.4%) were the common clinical features present among the patients. Out of these, only oliguria {odds ratio (OR) = 4.14 and 95% confidence interval (CI) 1.003-17.261}, jaundice (OR = 5.13 and 95% CI 1.149-28.003), and arrhythmias (OR = 5.774 and 95% CI 1.001-34.692), were predictors of myocarditis or acute renal failure and none of the laboratory measures could predict the two complications. Conclusions This study shows that out of clinical and laboratory variables, only oliguria, jaundice and arrhythmia are strong predictors of development of acute renal failure or myocarditis in patients with leptospirosis presented to Teaching Hospital of Kandy, Sri Lanka. PMID:22243770

[C1q/tumor necrosis factor related protein 6 (CTRP6) is involved in gentamicin-induced acute kidney injury in rats].

PubMed

Li, Rong; Yang, Xiaoxia; Yu, Yan; Zhou, Meilan; Tian, Xiujuan; Feng, Shidong; Wang, Hanmin

2016-11-01

Objective To explore the role of the anti-inflammatory cytokine C1q/tumor necrosis factor related protein 6 (CTRP6) in gentamicin-induced acute kidney injury in rats. Methods SD rats were divided into 5 groups including control group, model group and the other 3 experimental groups. The rats in model group and experimental groups were subcutaneously injected with gentamicin at the dose of 400 mg/(kg.d) for consecutive 2 days to induce acute renal injury. Two days before gentamicin injection, the rats in the 3 experimental groups were given pAd-CTRP6 at the doses of 0.5, 5 and 50 mg/kg, respectively. The serum levels of blood urea nitrogen (BUN) and creatinine (Cr) were respectively assayed with picric acid colorimetry and ultraviolet spectrophotometry; ELISA was used to detect serum CTRP6 content and the production of interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) in the kidney homogenate; Western blotting was performed to detect the expressions of CTRP6, caspase-1 and pyrin domain containing 3 (NLRP3) proteins in the renal tissues of rats. Results Compared with control group, serum BUN and Cr contents increased in the model rats; the secretion of inflammatory factors IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also enhanced in the model group. Compared with the model group, serum BUN and Cr contents decreased in the experimental groups; the secretion of IL-1β and TNF-α, as well as the expressions of caspase-1 and NLRP3 were also attenuated in the experimental groups. Moreover, with the increase of the injection dosage of pAd-CTRP6, the suppressive effect was gradually strengthened. Conclusion CTRP6 can attenuate gentamicin-induced acute renal injury in rats in a dose-dependent manner.

Cannabinoids & Stress: impact of HU-210 on behavioral tests of anxiety in acutely stressed mice.

PubMed

Kinden, Renee; Zhang, Xia

2015-05-01

Anxiety disorders are one of the most prevalent classes of mental disorders affecting the general population, but current treatment strategies are restricted by their limited efficacy and side effect profiles. Although the cannabinoid system is speculated to be a key player in the modulation of stress responses and emotionality, the vast majority of current research initiatives had not incorporated stress exposure into their experimental designs. This study was the first to investigate the impact of exogenous cannabinoid administration in an acutely stressed mouse model, where CD1 mice were pre-treated with HU-210, a potent CB1R agonist, prior to acute stress exposure and subsequent behavioral testing. Exogenous cannabinoid administration induced distinct behavioral phenotypes in stressed and unstressed mice. While low doses of HU-210 were anxiolytic in unstressed subjects, this effect was abolished when mice were exposed to an acute stressor. The administration of higher HU-210 doses in combination with acute stress exposure led to severe locomotor deficits that were not previously observed at the same dose in unstressed subjects. These findings suggest that exogenous cannabinoids and acute stress act synergistically in an anxiogenic manner. This study underlies the importance of including stress exposure into future anxiety-cannabinoid research due to the differential impact of cannabinoid administration on stressed and unstressed subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

[The Correlation Between MicroRNAs in Serum and the Extent of Liver Injury].

PubMed

Zuo, Yi-Nan; He, Xue-Ling; Shi, Xue-Ni; Wei, Shi-Hang; Yin, Hai-Lin

2017-05-01

To investigate the correlation between the absolute quantification of the microRNAs (miR-122, miR-451, miR-92a, miR-192) in serum during acute liver injury and the extent of liver injury on rat models of CCl 4 induced acute liver injury and mice models of acetaminophen (APAP) induced acute liver injury. Furthermore, to investigate the correlation between the absolute quantification of microRNAs in serum and the drug induced liver injury pathological scoring system (DILI-PSS). The acute liver injury model in rat by CCl 4 (1.5 mL/kg), and the acute liver injury model in mice by APAP (160 mg/kg) were established. The serum at different time points on both models were collected respectively. The absolute quantification of microRNAs in serum were detected by using MiRbay TM SV miRNA Assay kit. Meanwhile, the pathological sections of liver tissue of the mice at each time point were collected to analyze the correlation between microRNAs and the degree of liver injury. In CCl 4 -induced rat acute liver injury model and APAP induced mouse acute liver injury, miR-122 and miR-192 appeared to be rising significantly, which remained the highest level at 24 h after treatment, and declined to the normal level after 72 h. In CCl 4 -induced rat acute liver injury model, the change of miR-92a was fluctuated and had no apparent rules, miR-451 declined gradually, but not obviously. In mice acute liver injury model induced by APAP, miR-92a and miR-451 in the progress of liver injury declined gradually, reached the lowest point at 48 h, and then recovered. The result of correlation analysis indicated that miR-122 and miR-192 presented a good positive correlation with the DILI-PSS ( r =0.741 3, P <0.05; r =0.788 3, P <0.01). The absolute quantification of miR-122 and miR-192 in serum has the highest level in 24 h, then decrease in 72 h, in both drug-induced and chemical liver injury. In addition, both the two microRNAs have good correlation with DILI-PSS in APAP-induced liver injury models.

Role of Animal Models in Coronary Stenting.

PubMed

Iqbal, Javaid; Chamberlain, Janet; Francis, Sheila E; Gunn, Julian

2016-02-01

Coronary angioplasty initially employed balloon dilatation only. This technique revolutionized the treatment of coronary artery disease, although outcomes were compromised by acute vessel closure, late constrictive remodeling, and restenosis due to neointimal proliferation. These processes were studied in animal models, which contributed to understanding the biology of endovascular arterial injury. Coronary stents overcome acute recoil, with improvements in the design and metallurgy since then, leading to the development of drug-eluting stents and bioresorbable scaffolds. These devices now undergo computer modeling and benchtop and animal testing before evaluation in clinical trials. Animal models, including rabbit, sheep, dog and pig are available, all with individual benefits and limitations. In smaller mammals, such as mouse and rabbit, the target for stenting is generally the aorta; whereas in larger animals, such as the pig, it is generally the coronary artery. The pig coronary stenting model is a gold-standard for evaluating safety; but insights into biomechanical properties, the biology of stenting, and efficacy in controlling neointimal proliferation can also be gained. Intra-coronary imaging modalities such as intravascular ultrasound and optical coherence tomography allow precise serial evaluation in vivo, and recent developments in genetically modified animal models of atherosclerosis provide realistic test beds for future stents and scaffolds.

Low central venous pressure versus acute normovolemic hemodilution versus conventional fluid management for reducing blood loss in radical retropubic prostatectomy: a randomized controlled trial.

PubMed

Habib, Ashraf S; Moul, Judd W; Polascik, Thomas J; Robertson, Cary N; Roche, Anthony M; White, William D; Hill, Stephen E; Nosnick, Israel; Gan, Tong J

2014-05-01

To compare acute normovolemic hemodilution versus low central venous pressure strategy versus conventional fluid management in reducing intraoperative estimated blood loss, hematocrit drop and need for blood transfusion in patients undergoing radical retropubic prostatectomy under general anesthesia. Patients undergoing radical retropubic prostatectomy under general anesthesia were randomized to conventional fluid management, acute normovolemic hemodilution or low central venous pressure (≤5 mmHg). Treatment effects on estimated blood loss and hematocrit change were tested in multivariable regression models accounting for surgeon, prostate size, and all two-way interactions. Ninety-two patients completed the study. Estimated blood loss (mean ± SD) was significantly lower with low central venous pressure (706 ± 362 ml) compared to acute normovolemic hemodilution (1103 ± 635 ml) and conventional (1051 ± 714 ml) groups (p = 0.0134). There was no difference between the groups in need for blood transfusion, or hematocrit drop from preoperative values. The multivariate model predicting estimated blood loss showed a significant effect of treatment (p = 0.0028) and prostate size (p = 0.0323), accounting for surgeon (p = 0.0013). In the model predicting hematocrit change, accounting for surgeon difference (p = 0.0037), the treatment effect depended on prostate size (p = 0.0007) with the slope of low central venous pressure differing from the other two groups. Hematocrit was predicted to drop more with increased prostate size in acute normovolemic hemodilution and conventional groups but not with low central venous pressure. Limitations include the inability to blind providers to group assignment, possible variability between providers in estimation of blood loss, and the relatively small sample size that was not powered to detect differences between the groups in need for blood transfusion. Maintaining low central venous pressure reduced estimated blood loss compared to conventional fluid management and acute normovolemic hemodilution in patients undergoing radical retropubic prostatectomy but there was no difference in allogeneic blood transfusion between the groups.

Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0618 TITLE: Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury...Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience 5a. CONTRACT NUMBER...military and veterans. All persons with SCI are at increased risk of pressure ulcer development which remains one of the most significant secondary

Agent-based modeling of endotoxin-induced acute inflammatory response in human blood leukocytes.

PubMed

Dong, Xu; Foteinou, Panagiota T; Calvano, Steven E; Lowry, Stephen F; Androulakis, Ioannis P

2010-02-18

Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions. An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades. The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve our understanding of how manipulating the behavior of the molecular species could manifest into emergent behavior of the overall system.

Impact of managed care on the treatment, costs, and outcomes of fee-for-service Medicare patients with acute myocardial infarction.

PubMed

Bundorf, M Kate; Schulman, Kevin A; Stafford, Judith A; Gaskin, Darrell; Jollis, James G; Escarce, José J

2004-02-01

To examine the effects of market-level managed care activity on the treatment, cost, and outcomes of care for Medicare fee-for-service acute myocardial infarction (AMI) patients. Patients from the Cooperative Cardiovascular Project (CCP), a sample of Medicare beneficiaries discharged from nonfederal acute-care hospitals with a primary discharge diagnosis of AMI from January 1994 to February 1996. We estimated models of patient treatment, costs, and outcomes using ordinary least squares and logistic regression. The independent variables of primary interest were market-area managed care penetration and competition. The models included controls for patient, hospital, and other market area characteristics. We merged the CCP data with Medicare claims and other data sources. The study sample included CCP patients aged 65 and older who were admitted during 1994 and 1995 with a confirmed AMI to a nonrural hospital. Rates of revascularization and cardiac catheterization for Medicare fee-for-service patients with AMI are lower in high-HMO penetration markets than in low-penetration ones. Patients admitted in high-HMO-competition markets, in contrast, are more likely to receive cardiac catheterization for treatment of their AMI and had higher treatment costs than those admitted in low-competition markets. The level of managed care activity in the health care market affects the process of care for Medicare fee-for-service AMI patients. Spillovers from managed care activity to patients with other types of insurance are more likely when managed care organizations have greater market power.

Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms

PubMed Central

Burke, Richard D.; Todd, Spencer W.; Lumsden, Eric; Mullins, Roger J.; Mamczarz, Jacek; Fawcett, William P.; Gullapalli, Rao P.; Randall, William R.; Pereira, Edna F. R.; Albuquerque, Edson X.

2017-01-01

Organophosphorus (OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. PMID:28791702

The Role of Stress Regulation on Neural Plasticity in Pain Chronification.

PubMed

Li, Xiaoyun; Hu, Li

2016-01-01

Pain, especially chronic pain, is one of the most common clinical symptoms and has been considered as a worldwide healthcare problem. The transition from acute to chronic pain is accompanied by a chain of alterations in physiology, pathology, and psychology. Increasing clinical studies and complementary animal models have elucidated effects of stress regulation on the pain chronification via investigating activations of the hypothalamic-pituitary-adrenal (HPA) axis and changes in some crucial brain regions, including the amygdala, prefrontal cortex, and hippocampus. Although individuals suffer from acute pain benefit from such physiological alterations, chronic pain is commonly associated with maladaptive responses, like the HPA dysfunction and abnormal brain plasticity. However, the causal relationship among pain chronification, stress regulation, and brain alterations is rarely discussed. To call for more attention on this issue, we review recent findings obtained from clinical populations and animal models, propose an integrated stress model of pain chronification based on the existing models in perspectives of environmental influences and genetic predispositions, and discuss the significance of investigating the role of stress regulation on brain alteration in pain chronification for various clinical applications.

The Role of Stress Regulation on Neural Plasticity in Pain Chronification

PubMed Central

Li, Xiaoyun

2016-01-01

Pain, especially chronic pain, is one of the most common clinical symptoms and has been considered as a worldwide healthcare problem. The transition from acute to chronic pain is accompanied by a chain of alterations in physiology, pathology, and psychology. Increasing clinical studies and complementary animal models have elucidated effects of stress regulation on the pain chronification via investigating activations of the hypothalamic-pituitary-adrenal (HPA) axis and changes in some crucial brain regions, including the amygdala, prefrontal cortex, and hippocampus. Although individuals suffer from acute pain benefit from such physiological alterations, chronic pain is commonly associated with maladaptive responses, like the HPA dysfunction and abnormal brain plasticity. However, the causal relationship among pain chronification, stress regulation, and brain alterations is rarely discussed. To call for more attention on this issue, we review recent findings obtained from clinical populations and animal models, propose an integrated stress model of pain chronification based on the existing models in perspectives of environmental influences and genetic predispositions, and discuss the significance of investigating the role of stress regulation on brain alteration in pain chronification for various clinical applications. PMID:28053788

Cost-Effectiveness Analysis of Plasma Versus Recombinant Factor VIIa for Placing Intracranial Pressure Monitors in Pretransplant Patients With Acute Liver Failure.

PubMed

Pham, Huy P; Sireci, Anthony N; Kim, Chong H; Schwartz, Joseph

2014-09-01

Both plasma- and recombinant activated factor VII (rFVIIa)-based algorithms can be used to correct coagulopathy in preliver transplant patients with acute liver failure requiring intracranial pressure monitor (ICPM) placement. A decision model was created to compare the cost-effectiveness of these methods. A 70-kg patient could receive either 1 round of plasma followed by coagulation testing or 2 units of plasma and 40 μg/kg rFVIIa. Intracranial pressure monitor is placed without coagulation testing after rFVIIa administration. In the plasma algorithm, the probability of ICPM placement was estimated based on expected international normalized ratio (INR) after plasma administration. Risks of rFVIIa thrombosis and transfusion reactions were also included. The model was run for patients with INRs ranging from 2 to 6 with concomitant adjustments to model parameters. The model supported the initial use of rFVIIa for ICPM placement as a cost-effective treatment when INR ≥2 (with incremental cost-effectiveness ratio of at most US$7088.02). © The Author(s) 2014.

A Multi-factorial Model for Examining Racial and Ethnic Disparities in Acute Asthma Visits by Children

PubMed Central

Feldman, Jonathan M.; Serebrisky, Denise; Spray, Amanda

2012-01-01

Background Causes of children’s asthma health disparities are complex. Parents’ asthma illness representations may play a role. Purpose The study aims to test a theoretically based, multi-factorial model for ethnic disparities in children’s acute asthma visits through parental illness representations. Methods Structural equation modeling investigated the association of parental asthma illness representations, sociodemographic characteristics, health care provider factors, and social–environmental context with children’s acute asthma visits among 309 White, Puerto Rican, and African American families was conducted. Results Forty-five percent of the variance in illness representations and 30% of the variance in acute visits were accounted for. Statistically significant differences in illness representations were observed by ethnic group. Approximately 30% of the variance in illness representations was explained for whites, 23% for African Americans, and 26% for Puerto Ricans. The model accounted for >30% of the variance in acute visits for African Americans and Puerto Ricans but only 19% for the whites. Conclusion The model provides preliminary support that ethnic heterogeneity in asthma illness representations affects children’s health outcomes. PMID:22160799

Motivation to Quit Smoking after Acute Coronary Syndrome.

PubMed

Rocha, Vânia; Guerra, Marina; Lemos, Marina; Maciel, Júlia; Williams, Geoffrey

2017-01-31

Self-Determination Theory explores the process through which a person acquires motivation to initiate new behaviours related to health and to maintain them over time. This study aimed to determine the overall fit of Self-Determination Theory Model for Health Behavior to the data obtained from a sample of smokers hospitalized with acute coronary syndrome, and to identify the predictors of smoking status six months after clinical discharge. The sample included 110 participants, regular smokers, hospitalized due to acute coronary syndrome. Questionnaires were administered to assess autonomous self-regulation, perceived competence, family support, depressive symptoms and meaning in life. Participants were asked if they were currently smokers six months after clinical discharge. The results showed that the process variables specified by Self-Determination Theory fit the data well. Perceived competence predicted abstinence from smoking six months after clinical discharge. Our findings have similar characteristics to other international samples in which Self-Determination Theory models havebeen tested. It is important to facilitate perceived competence, as the patients who continue to smoke have shorter length of life. This study highlights the importance of considering clinical interventions based on Self-Determination Theory to facilitatesmoking cessation.

Necroptosis in Acute Kidney Injury.

PubMed

Anders, Hans-Joachim

2018-05-31

Regulated necrosis is an expanding research field with important implications for acute kidney injury (AKI). A focused review of the evolving evidence for necroptosis in AKI, one of several forms of regulated necrosis defines the known and unknown. A literature search was performed in PUBMED and ScienceDirect between January 1957 and April 2018 using the following keywords: "acute kidney injury," "necrosis," "necroptosis," "necroinflammation." The necroptosis signaling cascade involves a number of proteins including receptor-interacting protein-1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) as well as the MLKL regulator RGMb. The existing experimental evidence in AKI based on mice with genetic deletions of these proteins, more or less specific inhibitory compounds, and diverse experimental AKI models is reviewed. There is broad consistency suggesting a role for necroptosis in AKI, but some studies report divergent evidence potentially relating to the specific model used and the time point of analysis. Mlkl-deficient mice are currently the most specific and reliable experimental tool to study necroptosis in vivo (in kidney disease). The clinical potential of necroptosis inhibition in AKI is to be evaluated, but conceptual problems in AKI definitions and in complex clinical scenarios remain a concern. © 2018 S. Karger AG, Basel.

RNs and LPNs: emotional exhaustion and intention to leave.

PubMed

Havaei, Farinaz; MacPhee, Maura; Dahinten, V Susan

2016-04-01

To describe and compare registered nurse (RN) and licensed practical nurse (LPN) emotional exhaustion, intention to leave and reasons for leaving. Different skill mix/care delivery models are being used to address nurse shortages and rising health-care costs. Skill mix may include RNs and LPNs. More LPNs are being employed in areas, such as acute care, that have been previously staffed by all RNs. Little is known about nurse outcomes since the introduction of LPNs to acute care settings. This study was a cross-sectional correlational design. A stratified, random sample of acute care nurses completed surveys via Fluidsurveys. The survey was modelled after the RN4CAST nursing workforce survey. For both groups of nurses higher levels of emotional exhaustion were associated with intention to leave and workload was the most frequent reason cited for intention to leave. More RNs than LPNs cited career advancement as a reason to leave, and more LPNs than RNs identified poor salary as a reason to leave. Emotional exhaustion is linked to intention to leave health care. Nurse managers should address work environment factors associated with turnover intentions, such as professional development opportunities and shared decision-making. © 2015 John Wiley & Sons Ltd.

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection

PubMed Central

Lizardo, Kezia; Almonte, Vanessa; Law, Calvin; Aiyyappan, Janeesh Plakkal; Cui, Min-Hui; Nagajyothi, Jyothi F

2017-01-01

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi, which affects about 10 million people in its endemic regions of Latin America. After the initial acute stage of infection, 60–80% of infected individuals remain asymptomatic for several years to a lifetime; however, the rest develop the debilitating symptomatic stage, which affects the nervous system, digestive system and heart. The challenges of Chagas disease have become global due to immigration. Despite well documented dietary changes accompanying immigration, as well as a transition to a western style diet in the Chagas endemic regions, the role of host metabolism in the pathogenesis of Chagas disease remains underexplored. We have previously used a mouse model to show that host diet is a key factor regulating cardiomyopathy in Chagas disease. In this study we investigated the effect of a high fat diet on liver morphology and physiology, lipid metabolism, immune signaling, energy homeostasis, and stress responses in the murine model of acute T. cruzi infection. Our results indicate that in T. cruzi infected mice diet differentially regulates several liver processes, including autophagy, a stress response mechanism, with corresponding implications for human Chagas disease patients. PMID:27987056

A "multi-hit" model of neonatal white matter injury: cumulative contributions of chronic placental inflammation, acute fetal inflammation and postnatal inflammatory events.

PubMed

Korzeniewski, Steven J; Romero, Roberto; Cortez, Josepf; Pappas, Athina; Schwartz, Alyse G; Kim, Chong Jai; Kim, Jung-Sun; Kim, Yeon Mee; Yoon, Bo Hyun; Chaiworapongsa, Tinnakorn; Hassan, Sonia S

2014-11-01

We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a "multi-hit" model of neonatal white matter injury (WMI). This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) live-born singleton neonates delivered at Hutzel Women's Hospital, Detroit, MI, from 2006 to 2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation. A total of 425 live-born singleton neonates delivered before the 32nd week of gestation were included. Newborns delivered of pregnancies affected by chronic chorioamnionitis who had histologic evidence of an acute fetal inflammatory response were at increased risk of VE, unlike those without funisitis, relative to referent newborns without either condition, adjusting for gestational age [odds ratio (OR) 4.7; 95% confidence interval (CI) 1.4-15.8 vs. OR 1.3; 95% CI 0.7-2.6]. Similarly, newborns with funisitis who developed neonatal inflammation-initiating illness were at increased risk of VE, unlike those who did not develop such illness, compared to the referent group without either condition [OR 3.6 (95% CI 1.5-8.3) vs. OR 1.7 (95% CI 0.5-5.5)]. The greater the number of these three types of inflammation documented, the higher the risk of VE (P<0.0001). Chronic placental inflammation, acute fetal inflammation, and neonatal inflammation-initiating illness seem to interact in contributing risk information and/or directly damaging the developing brain of newborns delivered very preterm.

A ‘Multi-Hit’ Model of Neonatal White Matter Injury: Cumulative Contributions of Chronic Placental Inflammation, Acute Fetal Inflammation and Postnatal Inflammatory Events

PubMed Central

Korzeniewski, SJ; Romero, R; Cortez, J; Pappas, A; Schwartz, AG; Kim, CJ; Kim, JS; Kim, YM; Yoon, BH; Chaiworapongsa, T; Hassan, SS

2018-01-01

Objective We sought to determine whether cumulative evidence of perinatal inflammation was associated with increased risk in a ‘multi-hit’ model of neonatal white matter injury. Methods This retrospective cohort study included very preterm (gestational ages at delivery <32 weeks) liveborn singleton neonates delivered at Hutzel Women’s Hospital, Detroit, MI, from 2006–2011. Four pathologists blinded to clinical diagnoses and outcomes performed histological examinations according to standardized protocols. Neurosonography was obtained per routine clinical care. The primary indicator of WMI was ventriculomegaly (VE). Neonatal inflammation-initiating illnesses included bacteremia, surgical necrotizing enterocolitis, other infections, and those requiring mechanical ventilation. Results A total of 425 liveborn singleton neonates delivered before the 32nd week of gestation were included. Newborns delivered of pregnancies affected by chronic chorioamnionitis who had histologic evidence of an acute fetal inflammatory response were at increased risk of VE, unlike those without funisitis, relative to referent newborns without either condition, adjusting for gestational age [OR 4.7; 95%CI 1.4–15.8 vs. OR 1.3; 95%CI 0.7–2.6]. Similarly, newborns with funisitis who developed neonatal inflammation initiating illness were at increased risk of VE, unlike those who did not develop such illness, compared to the referent group without either condition [OR 3.6; 95%CI 1.5–8.3 vs. OR 1.7; 95%CI 0.5–5.5]. The greater the number of these three types of inflammation documented, the higher the risk of VE (p<0.0001). Conclusion Chronic placental inflammation, acute fetal inflammation and neonatal inflammation-initiating illness seem to interact in contributing risk information and/or directly damaging the developing brain of newborns delivered very preterm. PMID:25205706

Proposed Clinical Decision Rules to Diagnose Acute Rhinosinusitis Among Adults in Primary Care.

PubMed

Ebell, Mark H; Hansen, Jens Georg

2017-07-01

To reduce inappropriate antibiotic prescribing, we sought to develop a clinical decision rule for the diagnosis of acute rhinosinusitis and acute bacterial rhinosinusitis. Multivariate analysis and classification and regression tree (CART) analysis were used to develop clinical decision rules for the diagnosis of acute rhinosinusitis, defined using 3 different reference standards (purulent antral puncture fluid or abnormal finding on a computed tomographic (CT) scan; for acute bacterial rhinosinusitis, we used a positive bacterial culture of antral fluid). Signs, symptoms, C-reactive protein (CRP), and reference standard tests were prospectively recorded in 175 Danish patients aged 18 to 65 years seeking care for suspected acute rhinosinusitis. For each reference standard, we developed 2 clinical decision rules: a point score based on a logistic regression model and an algorithm based on a CART model. We identified low-, moderate-, and high-risk groups for acute rhinosinusitis or acute bacterial rhinosinusitis for each clinical decision rule. The point scores each had between 5 and 6 predictors, and an area under the receiver operating characteristic curve (AUROCC) between 0.721 and 0.767. For positive bacterial culture as the reference standard, low-, moderate-, and high-risk groups had a 16%, 49%, and 73% likelihood of acute bacterial rhinosinusitis, respectively. CART models had an AUROCC ranging from 0.783 to 0.827. For positive bacterial culture as the reference standard, low-, moderate-, and high-risk groups had a likelihood of acute bacterial rhinosinusitis of 6%, 31%, and 59% respectively. We have developed a series of clinical decision rules integrating signs, symptoms, and CRP to diagnose acute rhinosinusitis and acute bacterial rhinosinusitis with good accuracy. They now require prospective validation and an assessment of their effect on clinical and process outcomes. © 2017 Annals of Family Medicine, Inc.

Acute Lethality of Inhaled Hydrogen Cyanide in the Laboratory Rat: Impact of Concentration x Time Profile and Evaluation of the Predictivity of Toxic Load Models

DTIC Science & Technology

2013-05-03

public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...AVAILABILITY STATEMENT Approved for public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Toxic load models are mathematical...equal). The Department of Defense (DOD) (2005) publication “Potential Military Chemical/Biological Agents and Compounds” currently uses the toxic load

Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure.

PubMed

Ivanes, Fabrice; Susen, Sophie; Mouquet, Frédéric; Pigny, Pascal; Cuilleret, François; Sautière, Karine; Collet, Jean-Philippe; Beygui, Farzin; Hennache, Bernadette; Ennezat, Pierre Vladimir; Juthier, Françis; Richard, Florence; Dallongeville, Jean; Hillaert, Marieke A; Doevendans, Pieter A; Jude, Brigitte; Bertrand, Michel; Montalescot, Gilles; Van Belle, Eric

2012-01-01

Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001). Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

Income inequality and 30 day outcomes after acute myocardial infarction, heart failure, and pneumonia: retrospective cohort study.

PubMed

Lindenauer, Peter K; Lagu, Tara; Rothberg, Michael B; Avrunin, Jill; Pekow, Penelope S; Wang, Yongfei; Krumholz, Harlan M

2013-02-14

To examine the association between income inequality and the risk of mortality and readmission within 30 days of hospitalization. Retrospective cohort study of Medicare beneficiaries in the United States. Hierarchical, logistic regression models were developed to estimate the association between income inequality (measured at the US state level) and a patient's risk of mortality and readmission, while sequentially controlling for patient, hospital, other state, and patient socioeconomic characteristics. We considered a 0.05 unit increase in the Gini coefficient as a measure of income inequality. US acute care hospitals. Patients aged 65 years and older, and hospitalized in 2006-08 with a principal diagnosis of acute myocardial infarction, heart failure, or pneumonia. Risk of death within 30 days of admission or rehospitalization for any cause within 30 days of discharge. The potential number of excess deaths and readmissions associated with higher levels of inequality in US states in the three highest quarters of income inequality were compared with corresponding data in US states in the lowest quarter. Mortality analyses included 555,962 admissions (4348 hospitals) for acute myocardial infarction, 1,092,285 (4484) for heart failure, and 1,146,414 (4520); readmission analyses included 553,037 (4262), 1,345,909 (4494), and 1,345,909 (4524) admissions, respectively. In 2006-08, income inequality in US states (as measured by the average Gini coefficient over three years) varied from 0.41 in Utah to 0.50 in New York. Multilevel models showed no significant association between income inequality and mortality within 30 days of admission for patients with acute myocardial infarction, heart failure, or pneumonia. By contrast, income inequality was associated with rehospitalization (acute myocardial infarction, risk ratio 1.09 (95% confidence interval 1.03 to 1.15), heart failure 1.07 (1.01 to 1.12), pneumonia 1.09 (1.03 to 1.15)). Further adjustment for individual income and educational achievement did not significantly attenuate these findings. Over the three year period, we estimate an excess of 7153 (2297 to 11,733) readmissions for acute myocardial infarction, 17,991 (3410 to 31,772) for heart failure, and 14,127 (4617 to 23,115) for pneumonia, that are associated with inequality levels in US states in the three highest quarters of income inequality, compared with US states in the lowest quarter. Among patients hospitalized with acute myocardial infarction, heart failure, and pneumonia, exposure to higher levels of income inequality was associated with increased risk of readmission but not mortality. In view of the observational design of the study, these findings could be biased, owing to residual confounding.

Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

PubMed

Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

2014-09-01

Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. © 2014 by the Society for Experimental Biology and Medicine.

Assessing deep and shallow learning methods for quantitative prediction of acute chemical toxicity.

PubMed

Liu, Ruifeng; Madore, Michael; Glover, Kyle P; Feasel, Michael G; Wallqvist, Anders

2018-05-02

Animal-based methods for assessing chemical toxicity are struggling to meet testing demands. In silico approaches, including machine-learning methods, are promising alternatives. Recently, deep neural networks (DNNs) were evaluated and reported to outperform other machine-learning methods for quantitative structure-activity relationship modeling of molecular properties. However, most of the reported performance evaluations relied on global performance metrics, such as the root mean squared error (RMSE) between the predicted and experimental values of all samples, without considering the impact of sample distribution across the activity spectrum. Here, we carried out an in-depth analysis of DNN performance for quantitative prediction of acute chemical toxicity using several datasets. We found that the overall performance of DNN models on datasets of up to 30,000 compounds was similar to that of random forest (RF) models, as measured by the RMSE and correlation coefficients between the predicted and experimental results. However, our detailed analyses demonstrated that global performance metrics are inappropriate for datasets with a highly uneven sample distribution, because they show a strong bias for the most populous compounds along the toxicity spectrum. For highly toxic compounds, DNN and RF models trained on all samples performed much worse than the global performance metrics indicated. Surprisingly, our variable nearest neighbor method, which utilizes only structurally similar compounds to make predictions, performed reasonably well, suggesting that information of close near neighbors in the training sets is a key determinant of acute toxicity predictions.

Providing care for critically ill surgical patients: challenges and recommendations.

PubMed

Tisherman, Samuel A; Kaplan, Lewis; Gracias, Vicente H; Beilman, Gregory J; Toevs, Christine; Byrnes, Matthew C; Coopersmith, Craig M

2013-07-01

Providing optimal care for critically ill and injured surgical patients will become more challenging with staff shortages for surgeons and intensivists. This white paper addresses the historical issues behind the present situation, the need for all intensivists to engage in dedicated critical care per the intensivist model, and the recognition that intensivists from all specialties can provide optimal care for the critically ill surgical patient, particularly with continuing involvement by the surgeon of record. The new acute care surgery training paradigm (including trauma, surgical critical care, and emergency general surgery) has been developed to increase interest in trauma and surgical critical care, but the number of interested trainees remains too few. Recommendations are made for broadening the multidisciplinary training and practice opportunities in surgical critical care for intensivists from all base specialties and for maintaining the intensivist model within acute care surgery practice. Support from academic and administrative leadership, as well as national organizations, will be needed.

Cumulative dietary exposure to a selected group of pesticides of the triazole group in different European countries according to the EFSA guidance on probabilistic modelling.

PubMed

Boon, Polly E; van Donkersgoed, Gerda; Christodoulou, Despo; Crépet, Amélie; D'Addezio, Laura; Desvignes, Virginie; Ericsson, Bengt-Göran; Galimberti, Francesco; Ioannou-Kakouri, Eleni; Jensen, Bodil Hamborg; Rehurkova, Irena; Rety, Josselin; Ruprich, Jiri; Sand, Salomon; Stephenson, Claire; Strömberg, Anita; Turrini, Aida; van der Voet, Hilko; Ziegler, Popi; Hamey, Paul; van Klaveren, Jacob D

2015-05-01

The practicality was examined of performing a cumulative dietary exposure assessment according to the requirements of the EFSA guidance on probabilistic modelling. For this the acute and chronic cumulative exposure to triazole pesticides was estimated using national food consumption and monitoring data of eight European countries. Both the acute and chronic cumulative dietary exposures were calculated according to two model runs (optimistic and pessimistic) as recommended in the EFSA guidance. The exposures obtained with these model runs differed substantially for all countries, with the highest exposures obtained with the pessimistic model run. In this model run, animal commodities including cattle milk and different meat types, entered in the exposure calculations at the level of the maximum residue limit (MRL), contributed most to the exposure. We conclude that application of the optimistic model run on a routine basis for cumulative assessments is feasible. The pessimistic model run is laborious and the exposure results could be too far from reality. More experience with this approach is needed to stimulate the discussion of the feasibility of all the requirements, especially the inclusion of MRLs of animal commodities which seem to result in unrealistic conclusions regarding their contribution to the dietary exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diagnosis of Acute Appendicitis by Endoscopic Retrograde Appendicitis Therapy (ERAT): Combination of Colonoscopy and Endoscopic Retrograde Appendicography.

PubMed

Li, Yingchao; Mi, Chen; Li, Weizhi; She, Junjun

2016-11-01

Acute appendicitis is the most common abdominal emergency, but the diagnosis of appendicitis remains a challenge. Endoscopic retrograde appendicitis therapy (ERAT) is a new and minimally invasive procedure for the diagnosis and treatment of acute appendicitis. To investigate the diagnostic value of ERAT for acute appendicitis by the combination of colonoscopy and endoscopic retrograde appendicography (ERA). Twenty-one patients with the diagnosis of suspected uncomplicated acute appendicitis who underwent ERAT between November 2014 and January 2015 were included in this study. The main outcomes, imaging findings of acute appendicitis including colonoscopic direct-vision imaging and fluoroscopic ERA imaging, were retrospectively reviewed. Secondary outcomes included mean operative time, mean hospital stay, rate of complication, rate of appendectomy during follow-up period, and other clinical data. The diagnosis of acute appendicitis was established in 20 patients by positive ERA (5 patients) or colonoscopy (1 patient) alone or both (14 patients). The main colonoscopic imaging findings included mucosal inflammation (15/20, 75 %), appendicoliths (14/20, 70 %), and maturation (5/20, 25 %). The key points of ERA for diagnosing acute appendicitis included radiographic changes of appendix (17/20, 85 %), intraluminal appendicoliths (14/20, 70 %), and perforation (1/20, 5 %). Mean operative time of ERAT was 49.7 min, and mean hospital stay was 3.3 days. No patient converted to emergency appendectomy. Perforation occurred in one patient after appendicoliths removal was not severe and did not require invasive procedures. During at least 1-year follow-up period, only one patient underwent laparoscopic appendectomy. ERAT is a valuable procedure of choice providing a precise yield of diagnostic information for patients with suspected acute appendicitis by combination of colonoscopy and ERA.

Modeling the adenosine system as a modulator of cognitive performance and sleep patterns during sleep restriction and recovery

PubMed Central

Phillips, Andrew J. K.

2017-01-01

Sleep loss causes profound cognitive impairments and increases the concentrations of adenosine and adenosine A1 receptors in specific regions of the brain. Time courses for performance impairment and recovery differ between acute and chronic sleep loss, but the physiological basis for these time courses is unknown. Adenosine has been implicated in pathways that generate sleepiness and cognitive impairments, but existing mathematical models of sleep and cognitive performance do not explicitly include adenosine. Here, we developed a novel receptor-ligand model of the adenosine system to test the hypothesis that changes in both adenosine and A1 receptor concentrations can capture changes in cognitive performance during acute sleep deprivation (one prolonged wake episode), chronic sleep restriction (multiple nights with insufficient sleep), and subsequent recovery. Parameter values were estimated using biochemical data and reaction time performance on the psychomotor vigilance test (PVT). The model closely fit group-average PVT data during acute sleep deprivation, chronic sleep restriction, and recovery. We tested the model’s ability to reproduce timing and duration of sleep in a separate experiment where individuals were permitted to sleep for up to 14 hours per day for 28 days. The model accurately reproduced these data, and also correctly predicted the possible emergence of a split sleep pattern (two distinct sleep episodes) under these experimental conditions. Our findings provide a physiologically plausible explanation for observed changes in cognitive performance and sleep during sleep loss and recovery, as well as a new approach for predicting sleep and cognitive performance under planned schedules. PMID:29073206

Reassessment of HIV-1 acute phase infectivity: accounting for heterogeneity and study design with simulated cohorts.

PubMed

Bellan, Steve E; Dushoff, Jonathan; Galvani, Alison P; Meyers, Lauren Ancel

2015-03-01

The infectivity of the HIV-1 acute phase has been directly measured only once, from a retrospectively identified cohort of serodiscordant heterosexual couples in Rakai, Uganda. Analyses of this cohort underlie the widespread view that the acute phase is highly infectious, even more so than would be predicted from its elevated viral load, and that transmission occurring shortly after infection may therefore compromise interventions that rely on diagnosis and treatment, such as antiretroviral treatment as prevention (TasP). Here, we re-estimate the duration and relative infectivity of the acute phase, while accounting for several possible sources of bias in published estimates, including the retrospective cohort exclusion criteria and unmeasured heterogeneity in risk. We estimated acute phase infectivity using two approaches. First, we combined viral load trajectories and viral load-infectivity relationships to estimate infectivity trajectories over the course of infection, under the assumption that elevated acute phase infectivity is caused by elevated viral load alone. Second, we estimated the relative hazard of transmission during the acute phase versus the chronic phase (RHacute) and the acute phase duration (dacute) by fitting a couples transmission model to the Rakai retrospective cohort using approximate Bayesian computation. Our model fit the data well and accounted for characteristics overlooked by previous analyses, including individual heterogeneity in infectiousness and susceptibility and the retrospective cohort's exclusion of couples that were recorded as serodiscordant only once before being censored by loss to follow-up, couple dissolution, or study termination. Finally, we replicated two highly cited analyses of the Rakai data on simulated data to identify biases underlying the discrepancies between previous estimates and our own. From the Rakai data, we estimated RHacute = 5.3 (95% credibility interval [95% CrI]: 0.79-57) and dacute = 1.7 mo (95% CrI: 0.55-6.8). The wide credibility intervals reflect an inability to distinguish a long, mildly infectious acute phase from a short, highly infectious acute phase, given the 10-mo Rakai observation intervals. The total additional risk, measured as excess hazard-months attributable to the acute phase (EHMacute) can be estimated more precisely: EHMacute = (RHacute - 1) × dacute, and should be interpreted with respect to the 120 hazard-months generated by a constant untreated chronic phase infectivity over 10 y of infection. From the Rakai data, we estimated that EHMacute = 8.4 (95% CrI: -0.27 to 64). This estimate is considerably lower than previously published estimates, and consistent with our independent estimate from viral load trajectories, 5.6 (95% confidence interval: 3.3-9.1). We found that previous overestimates likely stemmed from failure to account for risk heterogeneity and bias resulting from the retrospective cohort study design. Our results reflect the interaction between the retrospective cohort exclusion criteria and high (47%) rates of censorship amongst incident serodiscordant couples in the Rakai study due to loss to follow-up, couple dissolution, or study termination. We estimated excess physiological infectivity during the acute phase from couples data, but not the proportion of transmission attributable to the acute phase, which would require data on the broader population's sexual network structure. Previous EHMacute estimates relying on the Rakai retrospective cohort data range from 31 to 141. Our results indicate that these are substantial overestimates of HIV-1 acute phase infectivity, biased by unmodeled heterogeneity in transmission rates between couples and by inconsistent censoring. Elevated acute phase infectivity is therefore less likely to undermine TasP interventions than previously thought. Heterogeneity in infectiousness and susceptibility may still play an important role in intervention success and deserves attention in future analyses.

Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

EPA Science Inventory

Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress.

PubMed

Parrott, Andy C

2006-03-01

Many recreational ecstasy/MDMA users display neuropsychobiological deficits, whereas others remain problem free. This review will investigate some of the drug and non-drug factors which influence the occurrence of these deficits. Acute and chronic MDMA usage are both important. Intensive use within a session is often associated with more problems. In term of lifetime usage, novice users generally remain unimpaired, whereas most heavy users report memory or other psychobiological problems which they attribute to ecstasy. These complaints are confirmed by objective deficits in working memory, attention, frontal-executive, and episodic memory tasks. Psychobiological deficits include disturbed sleep, sexual dysfunction, reduced immuno-competence, and increased oxidative stress. Further MDMA-related factors which may contribute to these changes, include acute and chronic tolerance, and drug dependence. Around 90ñ95% of ecstasy/MDMA users also take cannabis, and this can independently contribute to the adverse neuropsychobiological pro.les; although in some situations the acute co-use of these two drugs may be interactive rather than additive, since cannabis has relaxant and hypothermic properties. Alcohol, nicotine, amphetamine, and other drugs, can also affect the psychobiological pro.les of ecstasy polydrug users in complex ways. Pure MDMA users are rare but they have been shown to display significant neurocognitive deficits. Psychiatric aspects are debated in the context of the diathesis-stress model. Here the stressor of ecstasy polydrug drug use, interacts with various predisposition factors (genetic, neurochemical, personality), to determine the psychiatric outcome. Recreational MDMA is typically taken in hot and crowded dances/raves. Prolonged dancing, feeling hot, and raised body temperature, can also be associated with more psychobiological problems. This is consistent with the animal literature, where high ambient temperature and other metabolic stimulants boost the acute effects of MDMA, and cause greater serotonergic neurotoxicity. In conclusion, the neuropsychobiological effects of MDMA are modulated by a wide range of drug and non-drug factors. These multiple influences are integrated within a bioenergetic stress model, where factors which heighten acute metabolic distress lead to more neuropsychobiological problems.

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota

PubMed Central

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A.; Bereswill, Stefan

2017-01-01

Background Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Methodology/Principal findings Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. Conclusion/Significance With respect to the intestinal microbiota composition “humanized” mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation. PMID:28414794

Intestinal, extra-intestinal and systemic sequelae of Toxoplasma gondii induced acute ileitis in mice harboring a human gut microbiota.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Kühl, Anja A; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

Within seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction. Secondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum. With respect to the intestinal microbiota composition "humanized" mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation.

Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome.

PubMed

Maissen-Villiger, Carla A; Schweighauser, Ariane; van Dorland, H Anette; Morel, Claudine; Bruckmaier, Rupert M; Zurbriggen, Andreas; Francey, Thierry

2016-01-01

Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form. The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury. The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options for newer therapies targeting the identified pathways.

A retrospective study of ketamine administration and the development of acute or post-traumatic stress disorder in 274 war-wounded soldiers.

PubMed

Mion, G; Le Masson, J; Granier, C; Hoffmann, C

2017-12-01

The objective of this study was to explore whether ketamine prevents or exacerbates acute or post-traumatic stress disorders in military trauma patients. We conducted a retrospective study of a database from the French Military Health Service, including all soldiers surviving a war injury in Afghanistan (2010-2012). The diagnosis of post-traumatic stress disorder was made by a psychiatrist and patients were analysed according to the presence or absence of this condition. Analysis included the following covariables: age; sex; acute stress disorder; blast injury; associated fatality; brain injury; traumatic amputation; Glasgow coma scale; injury severity score; administered drugs; number of surgical procedures; physical, neurosensory or aesthetic sequelae; and the development chronic pain. Covariables related to post-traumatic and acute stress disorders with a p ≤ 0.10 were included in a multivariable logistic regression model. The data from 450 soldiers were identified; 399 survived, of which 274 were analysed. Among these, 98 (36%) suffered from post-traumatic stress disorder and 89 (32%) had received ketamine. Fifty-four patients (55%) in the post-traumatic stress disorder group received ketamine vs. 35 (20%) in the no PTSD group (p < 0.001). The 89 injured soldiers who received ketamine had a median (IQR [range]) injury severity score of 5 (3-13 [1-26]) vs. 3 (2-4 [1-6] in the 185 patients who did not (p < 0.001). At multivariable analysis, only acute stress disorder and total number of surgical procedures were independently associated with the development of post-traumatic stress disorder. In this retrospective study, ketamine administration was not a risk factor for the development of post-traumatic stress disorder in the military trauma setting. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

PubMed

Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

2017-01-01

Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.

PubMed

Cockrell, Adam S; Yount, Boyd L; Scobey, Trevor; Jensen, Kara; Douglas, Madeline; Beall, Anne; Tang, Xian-Chun; Marasco, Wayne A; Heise, Mark T; Baric, Ralph S

2016-11-28

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe pneumonia-like symptoms and multi-organ failure, with a case fatality rate of ∼36%. Limited clinical studies indicate that humans infected with MERS-CoV exhibit pathology consistent with the late stages of ARDS, which is reminiscent of the disease observed in patients infected with severe acute respiratory syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have been difficult to achieve, and small-animal models traditionally used to investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to modify the mouse genome to encode two amino acids (positions 288 and 330) that match the human sequence in the dipeptidyl peptidase 4 receptor, making mice susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in these engineered mice was then used to generate a mouse-adapted virus that replicated efficiently within the lungs and evoked symptoms indicative of severe ARDS, including decreased survival, extreme weight loss, decreased pulmonary function, pulmonary haemorrhage and pathological signs indicative of end-stage lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the engineered mice against MERS-CoV-induced ARDS.

Acute inhalative exposure assessment: derivation of guideline levels with special regard to sensitive subpopulations and time scaling.

PubMed

Mielke, Hans; Gundert, Anna; Abraham, Klaus; Gundert-Remy, Ursula

2005-10-30

Risk assessment for acute airborne exposure to volatile organic compounds (VOCs), including exposure to chemical warfare agents, requires consideration of local and systemic effects at high concentrations. The operating procedure developed by the US Acute Exposure Guideline Level (AEGL) committee has gained special attention, in part because of the international collaboration in the project. The procedure defines three levels (AEGL-1: discomfort; AEGL-2: irreversible or other serious, long-lasting adverse effects; AEGL-3: life-threatening effects or death) for different exposure times (10 and 30 min, and 1, 4 and 8 h). In this article, the methodology for deriving AEGL values is reported. Extending the areas covered by the existing AEGL methodology, sensitive subpopulations are dealt with in more detail. Sensitive persons are expected to suffer from stronger effects when exposed to a given external concentration. Using a kinetic model with the sample substance dichloromethane (DCM), the higher internal exposure of children is quantified and compared to a healthy, young adult. The difference is shown to depend on age, on dose, and on duration of exposure. Furthermore, several ways are presented to derive AEGL values for exposure times which differ from the exposure duration in animal studies ('time scaling'). In comparison to the conventional procedure, the alternative approaches are based on mechanistic models of the toxicodynamic effect. Use of these models results in AEGL values which are biologically justified.

Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis

PubMed Central

Lowes, D. A.; Webster, N. R.; Murphy, M. P.; Galley, H. F.

2013-01-01

Background Sepsis-induced organ failure is the major cause of death in critical care units, and is characterized by a massive dysregulated inflammatory response and oxidative stress. We investigated the effects of treatment with antioxidants that protect mitochondria (MitoQ, MitoE, or melatonin) in a rat model of lipopolysaccharide (LPS) plus peptidoglycan (PepG)-induced acute sepsis, characterized by inflammation, mitochondrial dysfunction and early organ damage. Methods Anaesthetized and ventilated rats received an i.v. bolus of LPS and PepG followed by an i.v. infusion of MitoQ, MitoE, melatonin, or saline for 5 h. Organs and blood were then removed for determination of mitochondrial and organ function, oxidative stress, and key cytokines. Results MitoQ, MitoE, or melatonin had broadly similar protective effects with improved mitochondrial respiration (P<0.002), reduced oxidative stress (P<0.02), and decreased interleukin-6 levels (P=0.0001). Compared with control rats, antioxidant-treated rats had lower levels of biochemical markers of organ dysfunction, including plasma alanine amino-transferase activity (P=0.02) and creatinine concentrations (P<0.0001). Conclusions Antioxidants that act preferentially in mitochondria reduce mitochondrial damage and organ dysfunction and decrease inflammatory responses in a rat model of acute sepsis. PMID:23381720

Appending Limited Clinical Data to an Administrative Database for Acute Myocardial Infarction Patients: The Impact on the Assessment of Hospital Quality.

PubMed

Hannan, Edward L; Samadashvili, Zaza; Cozzens, Kimberly; Jacobs, Alice K; Venditti, Ferdinand J; Holmes, David R; Berger, Peter B; Stamato, Nicholas J; Hughes, Suzanne; Walford, Gary

2016-05-01

Hospitals' risk-standardized mortality rates and outlier status (significantly higher/lower rates) are reported by the Centers for Medicare and Medicaid Services (CMS) for acute myocardial infarction (AMI) patients using Medicare claims data. New York now has AMI claims data with blood pressure and heart rate added. The objective of this study was to see whether the appended database yields different hospital assessments than standard claims data. New York State clinically appended claims data for AMI were used to create 2 different risk models based on CMS methods: 1 with and 1 without the added clinical data. Model discrimination was compared, and differences between the models in hospital outlier status and tertile status were examined. Mean arterial pressure and heart rate were both significant predictors of mortality in the clinically appended model. The C statistic for the model with the clinical variables added was significantly higher (0.803 vs. 0.773, P<0.001). The model without clinical variables identified 10 low outliers and all of them were percutaneous coronary intervention hospitals. When clinical variables were included in the model, only 6 of those 10 hospitals were low outliers, but there were 2 new low outliers. The model without clinical variables had only 3 high outliers, and the model with clinical variables included identified 2 new high outliers. Appending even a small number of clinical data elements to administrative data resulted in a difference in the assessment of hospital mortality outliers for AMI. The strategy of adding limited but important clinical data elements to administrative datasets should be considered when evaluating hospital quality for procedures and other medical conditions.

Assessment and provision of rehabilitation among patients hospitalized with acute ischemic stroke in China: Findings from the China National Stroke Registry II.

PubMed

Bettger, Janet Prvu; Li, Zixiao; Xian, Ying; Liu, Liping; Zhao, Xingquan; Li, Hao; Wang, Chunxue; Wang, Chunjuan; Meng, Xia; Wang, Anxin; Pan, Yuesong; Peterson, Eric D; Wang, Yilong; Wang, Yongjun

2017-04-01

Background Stroke rehabilitation improves functional recovery among stroke patients. However, little is known about clinical practice in China regarding the assessment and provision of rehabilitation among patients with acute ischemic stroke. Aims We examined the frequency and determinants of an assessment for rehabilitation among acute ischemic stroke patients from the China National Stroke Registry II. Methods Data for 19,294 acute ischemic stroke patients admitted to 219 hospitals from June 2012 to January 2013 were analyzed. The multivariable logistic regression model with the generalized estimating equation method accounting for in-hospital clustering was used to identify patient and hospital factors associated with having a rehabilitation assessment during the acute hospitalization. Results Among 19,294 acute ischemic stroke patients, 11,451 (59.4%) were assessed for rehabilitation. Rates of rehabilitation assessment varied among 219 hospitals (IQR 41.4% vs 81.5%). In the multivariable analysis, factors associated with increased likelihood of a rehabilitation assessment ( p < 0.05) included disability prior to stroke, higher NIHSS on admission, receipt of a dysphagia screen, deep venous thrombosis prophylaxis, carotid vessel imaging, longer length of stay, and treatment at a hospital with a higher number of hospital beds (per 100 units). In contrast, patients with a history of atrial fibrillation and hospitals with higher number of annual stroke discharges (per 100 patients) were less likely to receive rehabilitation assessment during the acute stroke hospitalization. Conclusions Rehabilitation assessment among acute ischemic stroke patients was suboptimal in China. Rates varied considerably among hospitals and support the need to improve adherence to recommended care for stroke survivors.

Interleukin-6 Induced "Acute" Phenotypic Microenvironment Promotes Th1 Anti-Tumor Immunity in Cryo-Thermal Therapy Revealed By Shotgun and Parallel Reaction Monitoring Proteomics.

PubMed

Xue, Ting; Liu, Ping; Zhou, Yong; Liu, Kun; Yang, Li; Moritz, Robert L; Yan, Wei; Xu, Lisa X

2016-01-01

Cryo-thermal therapy has been emerged as a promising novel therapeutic strategy for advanced breast cancer, triggering higher incidence of tumor regression and enhanced remission of metastasis than routine treatments. To better understand its anti-tumor mechanism, we utilized a spontaneous metastatic mouse model and quantitative proteomics to compare N-glycoproteome changes in 94 serum samples with and without treatment. We quantified 231 highly confident N-glycosylated proteins using iTRAQ shotgun proteomics. Among them, 53 showed significantly discriminated regulatory patterns over the time course, in which the acute phase response emerged as the most enhanced pathway. The anti-tumor feature of the acute response was further investigated using parallel reaction monitoring target proteomics and flow cytometry on 23 of the 53 significant proteins. We found that cryo-thermal therapy reset the tumor chronic inflammation to an "acute" phenotype, with up-regulation of acute phase proteins including IL-6 as a key regulator. The IL-6 mediated "acute" phenotype transformed IL-4 and Treg-promoting ICOSL expression to Th1-promoting IFN-γ and IL-12 production, augmented complement system activation and CD86(+)MHCII(+) dendritic cells maturation and enhanced the proliferation of Th1 memory cells. In addition, we found an increased production of tumor progression and metastatic inhibitory proteins under such "acute" environment, favoring the anti-metastatic effect. Moreover, cryo-thermal on tumors induced the strongest "acute" response compared to cryo/hyperthermia alone or cryo-thermal on healthy tissues, accompanying by the most pronounced anti-tumor immunological effect. In summary, we demonstrated that cryo-thermal therapy induced, IL-6 mediated "acute" microenvironment shifted the tumor chronic microenvironment from Th2 immunosuppressive and pro-tumorigenic to Th1 immunostimulatory and tumoricidal state. Moreover, the magnitude of "acute" and "danger" signals play a key role in determining the efficacy of anti-tumor activity.

Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.

PubMed

Li, Qin; Bi, Ming Jun; Bi, Wei Kang; Kang, Hai; Yan, Le Jing; Guo, Yun-Liang

2016-03-01

Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P < 0.01). Basal expressions of HO-1 and Nrf-2 proteins were found in normal brain tissue. CO poisoning could activate HO-1/Nrf-2 pathway, start oxidative stress response. After the administration of Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P < 0.01). These findings suggest that Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning. © 2014 Wiley Periodicals, Inc.

Preventive effects of interleukin-6 in lipopolysaccharide/d-galactosamine induced acute liver injury via regulating inflammatory response in hepatic macrophages.

PubMed

Li, Long; Duan, Chaoli; Zhao, Yan; Zhang, Xiaofang; Yin, Hongyan; Wang, Tianxi; Huang, Caoxin; Liu, Suhuan; Yang, Shuyu; Li, Xuejun

2017-10-01

Lipopolysaccharide/d-Galactosamine (LPS/d-Gal)-induced acute liver injury is characterized by significant inflammatory responses including TNF-α and interleukin-6 (IL-6) and is a widely applied experimental model for inflammation research. TNF-α is critical in the progression of LPS/d-Gal-induced liver injury. However, the role of IL-6 in this model is still unknown. In the present study, we aim to elucidate the involvement of IL-6 in the pathogenesis of acute liver injury induced by LPS/d-Gal in mice and its underlying mechanism. To induce acute liver injury, LPS (50μg/kg body weight) and d-Gal (400mg/kg body weight) were injected intraperitoneally in the C57BL/6 mice. The vehicle (saline) or a single dose of recombinant IL-6 (200μg/kg body weight) was administered 2h prior to LPS/d-Gal injection. Mice were sacrificed 2h and 6h after LPS/d-Gal injection. The results indicated that IL-6 treatment could protect mice from LPS/d-Gal-induced tissue damage, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, in vitro study showed that IL-6 treatment could significantly suppress LPS-triggered expression of proinflammatory cytokines and chemokines, TNF-α, RANTES and MCP-1 in macrophages while promoting the expression of M2 markers, such as Arg-1 and Mrc-1 in macrophages. Taken together, these findings revealed a novel and unexpected role of IL-6 in ameliorating LPS/d-Gal-induced acute liver injury via regulating inflammatory responses in hepatic macrophages. Copyright © 2017. Published by Elsevier B.V.

Falls in hospital and new placement in a nursing home among older people hospitalized with acute illness.

PubMed

Basic, David; Hartwell, Tabitha J

2015-01-01

To examine the association between falls in hospital and new placement in a nursing home among older people hospitalized with acute illness. This prospective cohort study of 2,945 consecutive patients discharged alive from an acute geriatric medicine service used multivariate logistic regression to model the association between one or more falls and nursing home placement (primary analysis). Secondary analyses stratified falls by injury and occurrence of multiple falls. Demographic, medical, and frailty measures were considered in adjusted models. The mean age of all patients was 82.8±7.6 years and 94% were admitted through the emergency department. During a median length of stay (LOS) of 11 days, 257 (8.7%) patients had a fall. Of these, 66 (25.7%) sustained an injury and 53 (20.6%) had two or more falls. Compared with nonfallers, fallers were more likely to be placed in a nursing home (odds ratio [OR]: 2.03, 95% confidence interval [CI]: 1.37-3.00), after adjustment for age, sex, frailty, and selected medical variables (including dementia and delirium). Patients without injury (OR: 1.83, 95% CI: 1.17-2.85) and those with injury (OR: 2.35, 95% CI: 1.15-4.77) were also more likely to be placed. Patients who fell had a longer LOS (median 19 days vs 10 days; P<0.001). This study of older people in acute care shows that falls in the hospital are significantly associated with new placement in a nursing home. Given the predominantly negative experiences and the financial costs associated with placement in a nursing home, fall prevention should be a high priority in older people hospitalized with acute illness.

Prediction of Tissue Outcome and Assessment of Treatment Effect in Acute Ischemic Stroke Using Deep Learning.

PubMed

Nielsen, Anne; Hansen, Mikkel Bo; Tietze, Anna; Mouridsen, Kim

2018-06-01

Treatment options for patients with acute ischemic stroke depend on the volume of salvageable tissue. This volume assessment is currently based on fixed thresholds and single imagine modalities, limiting accuracy. We wish to develop and validate a predictive model capable of automatically identifying and combining acute imaging features to accurately predict final lesion volume. Using acute magnetic resonance imaging, we developed and trained a deep convolutional neural network (CNN deep ) to predict final imaging outcome. A total of 222 patients were included, of which 187 were treated with rtPA (recombinant tissue-type plasminogen activator). The performance of CNN deep was compared with a shallow CNN based on the perfusion-weighted imaging biomarker Tmax (CNN Tmax ), a shallow CNN based on a combination of 9 different biomarkers (CNN shallow ), a generalized linear model, and thresholding of the diffusion-weighted imaging biomarker apparent diffusion coefficient (ADC) at 600×10 -6 mm 2 /s (ADC thres ). To assess whether CNN deep is capable of differentiating outcomes of ±intravenous rtPA, patients not receiving intravenous rtPA were included to train CNN deep, -rtpa to access a treatment effect. The networks' performances were evaluated using visual inspection, area under the receiver operating characteristic curve (AUC), and contrast. CNN deep yields significantly better performance in predicting final outcome (AUC=0.88±0.12) than generalized linear model (AUC=0.78±0.12; P =0.005), CNN Tmax (AUC=0.72±0.14; P <0.003), and ADC thres (AUC=0.66±0.13; P <0.0001) and a substantially better performance than CNN shallow (AUC=0.85±0.11; P =0.063). Measured by contrast, CNN deep improves the predictions significantly, showing superiority to all other methods ( P ≤0.003). CNN deep also seems to be able to differentiate outcomes based on treatment strategy with the volume of final infarct being significantly different ( P =0.048). The considerable prediction improvement accuracy over current state of the art increases the potential for automated decision support in providing recommendations for personalized treatment plans. © 2018 American Heart Association, Inc.

[Predictive factors of functional decline at hospital discharge in elderly patients hospitalised due to acute illness].

PubMed

Condorhuamán-Alvarado, Patricia Ysabel; Menéndez-Colino, Rocío; Mauleón-Ladrero, Coro; Díez-Sebastián, Jesús; Alarcón, Teresa; González-Montalvo, Juan Ignacio

To compare baseline characteristics and those found during hospitalisation as predictors of functional decline at discharge (FDd) in elderly patients hospitalised due to acute illness. A review was made of the computerized records of patients admitted to a Geriatric Acute Unit of a tertiary hospital over a 10 year period. A record was made of demographic, clinical, functional and health-care variables. Functional decline at discharge (FDd) was defined by the difference between the previous Barthel Index (pBI) and the discharge Barthel Index (dBI). The percentage of FDd (%FDd=(pBI-dBI/pBI)×100) was calculated. The variables associated with greater %FDd in the bivariate analysis were included in multivariate logistic regression models. The predictive capacity of each model was assessed using the area under the ROC curve. The factors associated with greater %FDd were advanced age, female gender, to live in a nursing home, cognitive impairment, better baseline functional status and worse functional status at admission, number of diagnoses, and prolonged stay. The area under the ROC curve for the predictive models of %FDd was 0.638 (95% CI: 0.615-0.662) based on the previous situation, 0.756 (95% CI: 0.736-0.776) based on the situation during admission, and 0.952 (95% CI: 0.944-0.959) based on a combination of these factors. The overall assessment of patient characteristics, both during admission and baseline, may have greater value in prediction of FDd than analysis of factors separately in elderly patients hospitalised due to acute illness. Copyright © 2017. Publicado por Elsevier España, S.L.U.

New activity-based funding model for Australian private sector overnight rehabilitation cases: the rehabilitation Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) model.

PubMed

Hanning, Brian; Predl, Nicolle

2015-09-01

Traditional overnight rehabilitation payment models in the private sector are not based on a rigorous classification system and vary greatly between contracts with no consideration of patient complexity. The payment rates are not based on relative cost and the length-of-stay (LOS) point at which a reduced rate applies (step downs) varies markedly. The rehabilitation Australian National Sub-Acute and Non-Acute Patient (AN-SNAP) model (RAM), which has been in place for over 2 years in some private hospitals, bases payment on a rigorous classification system, relative cost and industry LOS. RAM is in the process of being rolled out more widely. This paper compares and contrasts RAM with traditional overnight rehabilitation payment models. It considers the advantages of RAM for hospitals and Australian Health Service Alliance. It also considers payment model changes in the context of maintaining industry consistency with Electronic Claims Lodgement and Information Processing System Environment (ECLIPSE) and health reform generally.

REDUCING UNCERTAINTY IN AIR TOXICS RISK ASSESSMENT: A MECHANISTIC EXPOSURE-DOSE-RESPONSE (EDR) MODEL FOR ASSESSING THE ACUTE NEUROTOXICITY OF VOLATILE ORGANIC COMPOUNDS (VOCS) BASED UPON A RECEPTOR-MEDIATED MODE OF ACTION

EPA Science Inventory

SUMMARY: The major accomplishment of NTD’s air toxics program is the development of an exposure-dose- response model for acute exposure to volatile organic compounds (VOCs), based on momentary brain concentration as the dose metric associated with acute neurological impairments...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willemin, Marie-Emilie; Lumen, Annie, E-mail: Anni

Thyroid homeostasis can be disturbed due to thiocyanate exposure from the diet or tobacco smoke. Thiocyanate inhibits both thyroidal uptake of iodide, via the sodium-iodide symporter (NIS), and thyroid hormone (TH) synthesis in the thyroid, via thyroid peroxidase (TPO), but the mode of action of thiocyanate is poorly quantified in the literature. The characterization of the link between intra-thyroidal thiocyanate concentrations and dose of exposure is crucial for assessing the risk of thyroid perturbations due to thiocyanate exposure. We developed a PBPK model for thiocyanate that describes its kinetics in the whole-body up to daily doses of 0.15 mmol/kg, withmore » a mechanistic description of the thyroidal kinetics including NIS, passive diffusion, and TPO. The model was calibrated in a Bayesian framework using published studies in rats. Goodness-of-fit was satisfactory, especially for intra-thyroidal thiocyanate concentrations. Thiocyanate kinetic processes were quantified in vivo, including the metabolic clearance by TPO. The passive diffusion rate was found to be greater than NIS-mediated uptake rate. The model captured the dose-dependent kinetics of thiocyanate after acute and chronic exposures. Model behavior was evaluated using a Morris screening test. The distribution of thiocyanate into the thyroid was found to be determined primarily by the partition coefficient, followed by NIS and passive diffusion; the impact of the latter two mechanisms appears to increase at very low doses. Extrapolation to humans resulted in good predictions of thiocyanate kinetics during chronic exposure. The developed PBPK model can be used in risk assessment to quantify dose-response effects of thiocyanate on TH. - Highlights: • A PBPK model of thiocyanate (SCN{sup −}) was calibrated in rats in a Bayesian framework. • The intra-thyroidal kinetics of thiocyanate including NIS and TPO was modeled. • Passive diffusion rate for SCN{sup −} seemed to be greater than the NIS-mediated uptake. • The dose-dependent kinetics of SCN{sup −} was captured after an acute and chronic exposure. • The PBPK model of thiocyanate was successfully extrapolated to humans.« less

A multi-centre randomised trial to compare the effectiveness of geriatrician-led admission avoidance hospital at home versus inpatient admission.

PubMed

Shepperd, Sasha; Cradduck-Bamford, Andrea; Butler, Chris; Ellis, Graham; Godfrey, Mary; Gray, Alastair; Hemsley, Anthony; Khanna, Pradeep; Langhorne, Peter; McCaffrey, Patricia; Mirza, Lubena; Pushpangadan, Maj; Ramsay, Scott; Schiff, Rebekah; Stott, David; Young, John; Yu, Ly-Mee

2017-10-23

There is concern that existing models of acute hospital care will become unworkable as the health service admits an increasing number of frail older people with complex health needs, and that there is inadequate evidence to guide the planning of acute hospital level services. We aim to evaluate whether geriatrician-led admission avoidance to hospital at home is an effective alternative to hospital admission. We are conducting a multi-site randomised open trial of geriatrician-led admission avoidance hospital at home, compared with admission to hospital. We are recruiting older people with markers of frailty or prior dependence who have been referred to admission avoidance hospital at home for an acute medical event. This includes patients presenting with delirium, functional decline, dependence, falls, immobility or a background of dementia presenting with physical disease. Participants are randomised using a computerised random number generator to geriatrician-led admission avoidance hospital at home or a control group of inpatient admission in a 2:1 ratio in favour of the intervention. The primary endpoint 'living at home' (the inverse of death or living in a residential care setting) is measured at 6 months follow-up, and we also collect data on this outcome at 12 months. Secondary outcomes include the incidence of delirium, mortality, new long-term residential care, cognitive impairment, activities of daily living, quality of life and quality-adjusted survival, length of stay, readmission or transfer to hospital. We will conduct a parallel economic evaluation, and a process evaluation that includes an interview study to explore the experiences of patients and carers. Health systems around the world are examining how to provide acute hospital-level care to older adults in greater numbers with a fixed or shrinking hospital resource. This trial is the first large multi-site randomised trial of geriatrician-led admission avoidance hospital at home, and will provide evidence on alternative models of healthcare for older people who require hospital admission. ISRCTN60477865 : Registered on 10 March 2014. Trial Sponsor: University of Oxford. Version 3.1, 14/06/2016.

Outcomes of lower extremity bypass performed for acute limb ischemia

PubMed Central

Baril, Donald T.; Patel, Virendra I.; Judelson, Dejah R.; Goodney, Philip P.; McPhee, James T.; Hevelone, Nathanael D.; Cronenwett, Jack L.; Schanzer, Andres

2013-01-01

Objective Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. Methods All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Results Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function, and respiratory complications. Patients who underwent lower extremity bypass for acute limb ischemia had no difference in rates of graft occlusion (18.1% vs 18.5%; P = .77), but did have significantly higher rates of limb loss (22.4% vs 9.7%; P < .0001) and mortality (20.9% vs 13.1%; P < .0001) at 1 year. On multivariable analysis, acute limb ischemia was an independent predictor of both major amputation (hazard ratio, 2.16; confidence interval, 1.38–3.40; P = .001) and mortality (hazard ratio, 1.41; confidence interval, 1.09–1.83; P = .009) at 1 year. Conclusions Patients who present with acute limb ischemia represent a less medically optimized subgroup within the population of patients undergoing lower extremity bypass. These patients may be expected to have more complex operations followed by increased rates of perioperative adverse events. Additionally, despite equivalent graft patency rates, patients undergoing lower extremity bypass for acute ischemia have significantly higher rates of major amputation and mortality at 1 year. PMID:23714364

Outcomes of lower extremity bypass performed for acute limb ischemia.

PubMed

Baril, Donald T; Patel, Virendra I; Judelson, Dejah R; Goodney, Philip P; McPhee, James T; Hevelone, Nathanael D; Cronenwett, Jack L; Schanzer, Andres

2013-10-01

Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function, and respiratory complications. Patients who underwent lower extremity bypass for acute limb ischemia had no difference in rates of graft occlusion (18.1% vs 18.5%; P = .77), but did have significantly higher rates of limb loss (22.4% vs 9.7%; P < .0001) and mortality (20.9% vs 13.1%; P < .0001) at 1 year. On multivariable analysis, acute limb ischemia was an independent predictor of both major amputation (hazard ratio, 2.16; confidence interval, 1.38-3.40; P = .001) and mortality (hazard ratio, 1.41; confidence interval, 1.09-1.83; P = .009) at 1 year. Patients who present with acute limb ischemia represent a less medically optimized subgroup within the population of patients undergoing lower extremity bypass. These patients may be expected to have more complex operations followed by increased rates of perioperative adverse events. Additionally, despite equivalent graft patency rates, patients undergoing lower extremity bypass for acute ischemia have significantly higher rates of major amputation and mortality at 1 year. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Acute radiation risk models

NASA Astrophysics Data System (ADS)

Smirnova, Olga

Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.

Finding consensus on frailty assessment in acute care through Delphi method

PubMed Central

2016-01-01

Objective We seek to address gaps in knowledge and agreement around optimal frailty assessment in the acute medical care setting. Frailty is a common term describing older persons who are at increased risk of developing multimorbidity, disability, institutionalisation and death. Consensus has not been reached on the practical implementation of this concept to assess clinically and manage older persons in the acute care setting. Design Modified Delphi, via electronic questionnaire. Questions included ranking items that best recognise frailty, optimal timing, location and contextual elements of a successful tool. Intraclass correlation coefficients for overall levels of agreement, with consensus and stability tested by 2-way ANOVA with absolute agreement and Fisher's exact test. Participants A panel of national experts (academics, front-line clinicians and specialist charities) were invited to electronic correspondence. Results Variables reflecting accumulated deficit and high resource usage were perceived by participants as the most useful indicators of frailty in the acute care setting. The Acute Medical Unit and Care of the older Persons Ward were perceived as optimum settings for frailty assessment. ‘Clinically meaningful and relevant’, ‘simple (easy to use)’ and ‘accessible by multidisciplinary team’ were perceived as characteristics of a successful frailty assessment tool in the acute care setting. No agreement was reached on optimal timing, number of variables and organisational structures. Conclusions This study is a first step in developing consensus for a clinically relevant frailty assessment model for the acute care setting, providing content validation and illuminating contextual requirements. Testing on clinical data sets is a research priority. PMID:27742633

Risk factors for discharge to an acute care hospital from inpatient rehabilitation among stroke patients.

PubMed

Roberts, Pamela S; DiVita, Margaret A; Riggs, Richard V; Niewczyk, Paulette; Bergquist, Brittany; Granger, Carl V

2014-01-01

To identify medical and functional health risk factors for being discharged directly to an acute-care hospital from an inpatient rehabilitation facility among patients who have had a stroke. Retrospective cohort study. Academic medical center. A total of 783 patients with a primary diagnosis of stroke seen from 2008 to 2012; 60 were discharged directly to an acute-care hospital and 723 were discharged to other settings, including community and other institutional settings. Logistic regression analysis. Direct discharge to an acute care hospital compared with other discharge settings from the inpatient rehabilitation unit. No significant differences in demographic characteristics were found between the 2 groups. The adjusted logistic regression model revealed 2 significant risk factors for being discharged to an acute care hospital: admission motor Functional Independence Measure total score (odds ratio 0.97, 95% confidence interval 0.95-0.99) and enteral feeding at admission (odds ratio 2.87, 95% confidence interval 1.34-6.13). The presence of a Centers for Medicare and Medicaid-tiered comorbidity trended toward significance. Based on this research, we identified specific medical and functional health risk factors in the stroke population that affect the rate of discharge to an acute-care hospital. With active medical and functional management, early identification of these critical components may lead to the prevention of stroke patients from being discharged to an acute-care hospital from the inpatient rehabilitation setting. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Length of stay and medical stability for spinal cord-injured patients on admission to an inpatient rehabilitation hospital: a comparison between a model SCI trauma center and non-SCI trauma center.

PubMed

Ploumis, A; Kolli, S; Patrick, M; Owens, M; Beris, A; Marino, R J

2011-03-01

Retrospective database review. To compare lengths of stay (LOS), pressure ulcers and readmissions to the acute care hospital of patients admitted to the inpatient rehabilitation facility (IRF) from a model spinal cord injury (SCI) trauma center or from a non-SCI acute hospital. Only sparse data exist comparing the status of patients admitted to IRF from a model SCI trauma center or from a non-SCI acute hospital. Acute care, IRF and total LOS were compared between patients transferred to IRF from the SCI center (n=78) and from non-SCI centers (n=131). The percentages of pressure ulcers on admission to IRF and transfer back to acute care were also compared. Patients admitted to IRF from the SCI trauma center (SCI TC) had significantly shorter (P=0.01) acute care LOS and total LOS compared with patients admitted from non-SCI TCs. By neurological category, acute-care LOS was less for all groups admitted from the SCI center, but statistically significant only for tetraplegia. There was no significant difference in the incidence of readmissions to acute care from IRF. More patients from non-SCI centers (34%) than SCI centers (12%) had pressure ulcers (P<0.001). Acute care in organized SCI TCs before transfer to IRF can significantly lower acute-care LOS or total LOS and incidence of pressure ulcers compared with non-SCI TCs. Patients admitted to IRF from SCI TCs are no more likely to be sent back to an acute hospital than those from non-SCI TCs.

Involvements of γδT Lymphocytes in Acute and Chronic Skin Wound Repair.

PubMed

Xu, Peng; Fu, Xiujun; Xiao, Nin; Guo, Yuanyuan; Pei, Qing; Peng, Yinbo; Zhang, Yifan; Yao, Min

2017-08-01

Wound healing involves three stages including inflammation, proliferation, and tissue remodeling. The underlying mechanisms remain to be further elucidated. The inflammation is characterized by spatially and temporally changing patterns of various leukocyte subsets. It is regarded as the most crucial stage since the inflammatory response is instrumental to supplying various factors and cytokines that orchestrate healing events. As a subtype of T lymphocytes, γδ T cells play an important role in skin homeostasis, tumor immunosurveillance, and wound repair. However, either the dynamics of γδ T cells in healing process or the anticipated association of γδ T cells with chronic or refractory wounds were not well understood. In this study, we determine the dynamics of γδ T cells and γδ T cell-produced effectors during acute and chronic wound repair by establishing a third-degree burn model in mice skin or human skin from diabetic patients. Our data show that the involvement of γδ T cells in acute and chronic skin wound healing. The protein levels and mRNA expressions of γδ T cell-produced effectors were increased in acute healing model, whereas those effectors were decreased in chronic repair, suggesting γδ T cells are essential for wound repair. This study probes into the significant relevance of γδ T cells with effective wound repair and provides new enlightenments for the mechanisms of the formation of chronic and/or refractory wounds.

A fast multiparameter MRI approach for acute stroke assessment on a 3T clinical scanner: preliminary results in a non-human primate model with transient ischemic occlusion.

PubMed

Zhang, Xiaodong; Tong, Frank; Li, Chun-Xia; Yan, Yumei; Nair, Govind; Nagaoka, Tsukasa; Tanaka, Yoji; Zola, Stuart; Howell, Leonard

2014-04-01

Many MRI parameters have been explored and demonstrated the capability or potential to evaluate acute stroke injury, providing anatomical, microstructural, functional, or neurochemical information for diagnostic purposes and therapeutic development. However, the application of multiparameter MRI approach is hindered in clinic due to the very limited time window after stroke insult. Parallel imaging technique can accelerate MRI data acquisition dramatically and has been incorporated in modern clinical scanners and increasingly applied for various diagnostic purposes. In the present study, a fast multiparameter MRI approach including structural T1-weighted imaging (T1W), T2-weighted imaging (T2W), diffusion tensor imaging (DTI), T2-mapping, proton magnetic resonance spectroscopy, cerebral blood flow (CBF), and magnetization transfer (MT) imaging, was implemented and optimized for assessing acute stroke injury on a 3T clinical scanner. A macaque model of transient ischemic stroke induced by a minimal interventional approach was utilized for evaluating the multiparameter MRI approach. The preliminary results indicate the surgical procedure successfully induced ischemic occlusion in the cortex and/or subcortex in adult macaque monkeys (n=4). Application of parallel imaging technique substantially reduced the scanning duration of most MRI data acquisitions, allowing for fast and repeated evaluation of acute stroke injury. Hence, the use of the multiparameter MRI approach with up to five quantitative measures can provide significant advantages in preclinical or clinical studies of stroke disease.

Acute Kidney Injury and Subsequent Frailty Status in Survivors of Critical Illness: A Secondary Analysis.

PubMed

Abdel-Kader, Khaled; Girard, Timothy D; Brummel, Nathan E; Saunders, Christina T; Blume, Jeffrey D; Clark, Amanda J; Vincz, Andrew J; Ely, E Wesley; Jackson, James C; Bell, Susan P; Archer, Kristin R; Ikizler, T Alp; Pandharipande, Pratik P; Siew, Edward D

2018-05-01

Acute kidney injury frequently complicates critical illness and is associated with high morbidity and mortality. Frailty is common in critical illness survivors, but little is known about the impact of acute kidney injury. We examined the association of acute kidney injury and frailty within a year of hospital discharge in survivors of critical illness. Secondary analysis of a prospective cohort study. Medical/surgical ICU of a U.S. tertiary care medical center. Three hundred seventeen participants with respiratory failure and/or shock. None. Acute kidney injury was determined using Kidney Disease Improving Global Outcomes stages. Clinical frailty status was determined using the Clinical Frailty Scale at 3 and 12 months following discharge. Covariates included mean ICU Sequential Organ Failure Assessment score and Acute Physiology and Chronic Health Evaluation II score as well as baseline comorbidity (i.e., Charlson Comorbidity Index), kidney function, and Clinical Frailty Scale score. Of 317 patients, 243 (77%) had acute kidney injury and one in four patients with acute kidney injury was frail at baseline. In adjusted models, acute kidney injury stages 1, 2, and 3 were associated with higher frailty scores at 3 months (odds ratio, 1.92; 95% CI, 1.14-3.24; odds ratio, 2.40; 95% CI, 1.31-4.42; and odds ratio, 4.41; 95% CI, 2.20-8.82, respectively). At 12 months, a similar association of acute kidney injury stages 1, 2, and 3 and higher Clinical Frailty Scale score was noted (odds ratio, 1.87; 95% CI, 1.11-3.14; odds ratio, 1.81; 95% CI, 0.94-3.48; and odds ratio, 2.76; 95% CI, 1.34-5.66, respectively). In supplemental and sensitivity analyses, analogous patterns of association were observed. Acute kidney injury in survivors of critical illness predicted worse frailty status 3 and 12 months postdischarge. These findings have important implications on clinical decision making among acute kidney injury survivors and underscore the need to understand the drivers of frailty to improve patient-centered outcomes.

Risk factors for repeat adverse asthma events in children after visiting an emergency department.

PubMed

To, Teresa; Wang, Chengning; Dell, Sharon; Fleming-Carroll, Bonnie; Parkin, Patricia; Scolnik, Dennis; Ungar, Wendy

2008-01-01

The aim of this study was to identify risk factors for long-term adverse outcomes in children with asthma after visiting the emergency department (ED). A prospective observational study was conducted at the ED of a pediatric tertiary hospital in Ontario, Canada. Patient outcomes (ie, acute asthma episodes and ED visits) were measured at baseline and at 1- and 6-months post-ED discharge. Time trends in outcomes were assessed using the generalized estimating equations method. Multiple conditional logistic regressions were used to model outcomes at 6 months and examine the impact of drug insurance coverage while adjusting for confounders. Of the 269 children recruited, 81.8% completed both follow-ups. ED use significantly reduced from 39.4% at baseline to 26.8% at 6 months (P < .001), whereas the level of acute asthma episodes remained unchanged. Children with drug insurance coverage were less likely to have acute asthma episodes (adjusted odds ratio [AOR] = 0.36; 95% CI, 0.15-0.85; P < .02) or repeat ED visits (AOR = 0.45; 95% CI, 0.20-0.99; P < .05) at 6 months. Other risk factors for adverse outcomes included previous adverse asthma events and certain asthma triggers (eg, cold/sinus infection). Washing bed linens in hot water weekly was protective against subsequent acute asthma episodes. Our study demonstrated significant improvements in long-term outcomes in children seeking acute care for asthma in the ED. Future efforts remain in targeting the sustainability of improved outcomes beyond 6 months. Risk factors identified can help target vulnerable populations for proper interventions, which may include efforts to maximize insurance coverage for asthma medications and strategies to improve asthma self-management through patient and provider education.

The measurable cost of complications for outpatient cosmetic surgery in patients with mental health diagnoses.

PubMed

Wimalawansa, Sunishka M; Fox, Justin P; Johnson, R Michael

2014-02-01

Mental health conditions, including psychiatric and substance abuse diagnoses, have been associated with poor postoperative outcomes, but no studies have quantified the relationship to date. The authors examine the association between mental health conditions and immediate postoperative outcomes as defined by further hospital-based acute care within 30 days of surgery. California State Ambulatory Surgery, Inpatient, and Emergency Department Databases were used to identify all adult patients undergoing outpatient cosmetic plastic surgery between January 2007 and October 2011. Patients were subgrouped by the presence of mental health or substance abuse conditions. Primary outcome was the need for hospital-based acute care (admission or emergency department visit) within 30 days after surgery. Multivariable logistic regression models compared outcomes between groups. Of 116,597 patients meeting inclusion criteria, 3.9% and 1.4% had either a psychiatric or substance abuse diagnosis, respectively. Adjusting for medical comorbidities, patients with psychiatric disorders more frequently required hospital-based acute care within 30 days postoperatively than those without mental illness diagnoses (11.1% vs 3.6%; adjusted odds ratio [AOR], 1.78 [95% confidence interval, 1.59-1.99]). This was true both for hospital admissions (3.5% vs 1.1%; AOR, 1.61 [1.32-1.95]) and emergency department visits (8.8% vs 2.7%; AOR, 1.88 [1.66-2.14]). The most common acute diagnoses were surgical in nature, including postoperative infection, hemorrhage, and hematoma; the median hospital admission charge was $35 637. Similar findings were noted among patients with a substance abuse diagnosis. Mental health conditions are independently associated with the need for more frequent hospital-based acute care following surgery, thus contributing to added costs of care. A patient's mental health should be preoperatively assessed and appropriately addressed before proceeding with any elective procedure. 4.

Serum Acylcarnitines and Risk of Cardiovascular Death and Acute Myocardial Infarction in Patients With Stable Angina Pectoris.

PubMed

Strand, Elin; Pedersen, Eva R; Svingen, Gard F T; Olsen, Thomas; Bjørndal, Bodil; Karlsson, Therese; Dierkes, Jutta; Njølstad, Pål R; Mellgren, Gunnar; Tell, Grethe S; Berge, Rolf K; Svardal, Asbjørn; Nygård, Ottar

2017-02-03

Excess levels of serum acylcarnitines, which are intermediate products in metabolism, have been observed in metabolic diseases such as type 2 diabetes mellitus. However, it is not known whether acylcarnitines may prospectively predict risk of cardiovascular death or acute myocardial infarction in patients with stable angina pectoris. This study included 4164 patients (median age, 62 years; 72% men). Baseline serum acetyl-, octanoyl-, palmitoyl-, propionyl-, and (iso)valerylcarnitine were measured using liquid chromatography/tandem mass spectrometry. Hazard ratios (HRs) and 95% CIs for quartile 4 versus quartile 1 are reported. The multivariable model included age, sex, body mass index, fasting status, current smoking, diabetes mellitus, apolipoprotein A1, apolipoprotein B, creatinine, left ventricular ejection fraction, extent of coronary artery disease, study center, and intervention with folic acid or vitamin B6. During median 10.2 years of follow-up, 10.0% of the patients died of cardiovascular disease and 12.8% suffered a fatal or nonfatal acute myocardial infarction. Higher levels of the even-chained acetyl-, octanoyl-, and palmitoyl-carnitines were significantly associated with elevated risk of cardiovascular death, also after multivariable adjustments (HR [95% CI]: 1.52 [1.12, 2.06]; P=0.007; 1.73 [1.23, 2.44]; P=0.002; and 1.61 [1.18, 2.21]; P=0.003, respectively), whereas their associations with acute myocardial infarction were less consistent. Among patients with suspected stable angina pectoris, elevated serum even-chained acylcarnitines were associated with increased risk of cardiovascular death and, to a lesser degree with acute myocardial infarction, independent of traditional risk factors. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00354081. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Acute kidney failure

MedlinePlus

Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

The effect of olanzapine pretreatment on acute cocaine toxicity in mice.

PubMed

Heard, Kennon J; Cleveland, Nathan R; Krier, Shay

2009-07-01

Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

Spontaneous asymptomatic gallbladder perforation

PubMed Central

Seçil, Mustafa

2014-01-01

Gallstone disease is common. However, a proportion of patients are asymptomatic and remain undiagnosed until the occurrence of complications. Common complications include acute cholecystitis, biliary obstruction, acute pancreatitis and cholangitis. Severe complications include gallbladder perforation, Mirizzi syndrome and fistula formation are usually associated with significant morbidity and mortality. We report a case of asymptomatic spotaneous gallbladder perforation due to acute cholecystitis. PMID:24914424

Utilization of ICU Data to Improve 30 and 60 Day Mortality Models

DTIC Science & Technology

2017-01-06

Acute Radiation Syndrome , Mortality, Burn Combined Injury, Lethality, Small Intestine, Ordinary Differential...short period of time (high dose rate) causes acute radiation syndrome (ARS). Depending on the radiation dose, an individual may experience the...hematopoietic acute radiation syndrome (H-ARS) or the gastrointestinal acute radiation syndrome (GI-ARS) (reviewed in Maciàă I Garau et al., 2011). For acute

WE-EF-207-03: Design and Optimization of a CBCT Head Scanner for Detection of Acute Intracranial Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, J; Sisniega, A; Zbijewski, W

Purpose: To design a dedicated x-ray cone-beam CT (CBCT) system suitable to deployment at the point-of-care and offering reliable detection of acute intracranial hemorrhage (ICH), traumatic brain injury (TBI), stroke, and other head and neck injuries. Methods: A comprehensive task-based image quality model was developed to guide system design and optimization of a prototype head scanner suitable to imaging of acute TBI and ICH. Previously reported models were expanded to include the effects of x-ray scatter correction necessary for detection of low contrast ICH and the contribution of bit depth (digitization noise) to imaging performance. Task-based detectablity index provided themore » objective function for optimization of system geometry, x-ray source, detector type, anti-scatter grid, and technique at 10–25 mGy dose. Optimal characteristics were experimentally validated using a custom head phantom with 50 HU contrast ICH inserts imaged on a CBCT imaging bench allowing variation of system geometry, focal spot size, detector, grid selection, and x-ray technique. Results: The model guided selection of system geometry with a nominal source-detector distance 1100 mm and optimal magnification of 1.50. Focal spot size ∼0.6 mm was sufficient for spatial resolution requirements in ICH detection. Imaging at 90 kVp yielded the best tradeoff between noise and contrast. The model provided quantitation of tradeoffs between flat-panel and CMOS detectors with respect to electronic noise, field of view, and readout speed required for imaging of ICH. An anti-scatter grid was shown to provide modest benefit in conjunction with post-acquisition scatter correction. Images of the head phantom demonstrate visualization of millimeter-scale simulated ICH. Conclusions: Performance consistent with acute TBI and ICH detection is feasible with model-based system design and robust artifact correction in a dedicated head CBCT system. Further improvements can be achieved with incorporation of model-based iterative reconstruction techniques also within the scope of the task-based optimization framework. David Foos and Xiaohui Wang are employees of Carestream Health.« less

A Quantitative Quasispecies Theory-Based Model of Virus Escape Mutation Under Immune Selection

DTIC Science & Technology

2012-01-01

immune pressure, and their capacity for rapid escape mutation underlies many of the difficulties in combating pathogens, including HIV -1. In a typical...interpreted as the total number of virions within a finite sys- tem. The HIV -1 viral load during the acute infection phase can reach up to 104 ∼ 106...therefore models both the de- crease of the mean fitness away from WT and the distribution of neutral, deleterious, and beneficial mutants for a

Symptomatic Avascular Necrosis: An Understudied Risk Factor for Acute Care Utilization by Patients with SCD

PubMed Central

Yu, Tiffany; Campbell, Timothy; Ciuffetelli, Isabella; Haywood, Carlton; Carroll, C. Patrick; Resar, Linda M.S.; Strouse, John J.; Lanzkron, Sophie

2016-01-01

Objectives Sickle cell disease (SCD) is associated with high healthcare utilization rates and poor outcomes in a subset of patients, although the underlying factors that predict this phenotype are poorly understood. Prior studies suggest that comorbid avascular necrosis (AVN) contributes to high healthcare utilization. We sought to clarify whether AVN independently predicts acute care utilization in adults with SCD and to identify characteristics of those with AVN that predict higher utilization. Methods We reviewed the medical records of 87 patients with SCD with symptomatic AVN and compared acute care utilization and clinical characteristics with 87 sex- and age-matched patients with SCD without symptomatic AVN. Patients with ≥2 years of follow-up were included. Outcomes were compared using bivariate analysis and multivariate regression. Results Our study included 1381 follow-up years, with a median of 7 years per patient. The AVN cohort had greater median rates of urgent care visits (3.2/year vs 1.3/year; P = 0.0155), admissions (1.3/year vs 0.4/year; P = 0.0002), and admission days (5.1 days/year vs 1.8 days/year; P = 0.0007). History of high utilization (odds ratio [OR] 4.28; P = 0.001), acute chest syndrome (OR 3.12; P = 0.005), pneumonia (OR 3.20; P = 0.023), hydroxyurea therapy (OR 2.23; P = 0.0136), and long-term transfusion (OR 2.33; P = 0.014) were associated with AVN. In a median regression model, AVN, acute chest syndrome, and pneumonia were independently associated with greater urgent care visits and admissions. Conclusions Symptomatic AVN was found to be an independent risk factor for acute care utilization in patients with SCD. Because this is a potentially modifiable factor, further studies are urgently needed to determine whether AVN prevention/early treatment interventions will alter utilization and improve outcomes for patients with SCD. PMID:27598353

Symptomatic Avascular Necrosis: An Understudied Risk Factor for Acute Care Utilization by Patients with SCD.

PubMed

Yu, Tiffany; Campbell, Timothy; Ciuffetelli, Isabella; Haywood, Carlton; Carroll, Christopher Patrick; Resar, Linda; Strouse, John J; Lanzkron, Sophie

2016-09-01

Sickle cell disease (SCD) is associated with high healthcare utilization rates and poor outcomes in a subset of patients, although the underlying factors that predict this phenotype are poorly understood. Prior studies suggest that comorbid avascular necrosis (AVN) contributes to high healthcare utilization. We sought to clarify whether AVN independently predicts acute care utilization in adults with SCD and to identify characteristics of those with AVN that predict higher utilization. We reviewed the medical records of 87 patients with SCD with symptomatic AVN and compared acute care utilization and clinical characteristics with 87 sex- and age-matched patients with SCD without symptomatic AVN. Patients with ≥2 years of follow-up were included. Outcomes were compared using bivariate analysis and multivariate regression. Our study included 1381 follow-up years, with a median of 7 years per patient. The AVN cohort had greater median rates of urgent care visits (3.2/year vs 1.3/year; P = 0.0155), admissions (1.3/year vs 0.4/year; P = 0.0002), and admission days (5.1 days/year vs 1.8 days/year; P = 0.0007). History of high utilization (odds ratio [OR] 4.28; P = 0.001), acute chest syndrome (OR 3.12; P = 0.005), pneumonia (OR 3.20; P = 0.023), hydroxyurea therapy (OR 2.23; P = 0.0136), and long-term transfusion (OR 2.33; P = 0.014) were associated with AVN. In a median regression model, AVN, acute chest syndrome, and pneumonia were independently associated with greater urgent care visits and admissions. Symptomatic AVN was found to be an independent risk factor for acute care utilization in patients with SCD. Because this is a potentially modifiable factor, further studies are urgently needed to determine whether AVN prevention/early treatment interventions will alter utilization and improve outcomes for patients with SCD.

Control of acute, chronic, and constitutive hyperammonemia by wild-type and genetically engineered Lactobacillus plantarum in rodents.

PubMed

Nicaise, Charles; Prozzi, Deborah; Viaene, Eric; Moreno, Christophe; Gustot, Thierry; Quertinmont, Eric; Demetter, Pieter; Suain, Valérie; Goffin, Philippe; Devière, Jacques; Hols, Pascal

2008-10-01

Hyperammonemia is a common complication of acute and chronic liver diseases. Often accompanied with side effects, therapeutic interventions such as antibiotics or lactulose are generally targeted to decrease the intestinal production and absorption of ammonia. In this study, we aimed to modulate hyperammonemia in three rodent models by administration of wild-type Lactobacillus plantarum, a genetically engineered ammonia hyperconsuming strain, and a strain deficient for the ammonia transporter. Wild-type and metabolically engineered L. plantarum strains were administered in ornithine transcarbamoylase-deficient Sparse-fur mice, a model of constitutive hyperammonemia, in a carbon tetrachloride rat model of chronic liver insufficiency and in a thioacetamide-induced acute liver failure mice model. Constitutive hyperammonemia in Sparse-fur mice and hyperammonemia in a rat model of chronic hepatic insufficiency were efficiently decreased by Lactobacillus administration. In a murine thioacetamide-induced model of acute liver failure, administration of probiotics significantly increased survival and decreased blood and fecal ammonia. The ammonia hyperconsuming strain exhibited a beneficial effect at a lower dose than its wild-type counterpart. Improved survival in the acute liver failure mice model was associated with lower blood ammonia levels but also with a decrease of astrocyte swelling in the brain cortex. Modulation of ammonia was abolished after administration of the strain deficient in the ammonium transporter. Intestinal pH was clearly lowered for all strains and no changes in gut flora were observed. Hyperammonemia in constitutive model or after acute or chronic induced liver failure can be controlled by the administration of L. plantarum with a significant effect on survival. The mechanism involved in this ammonia decrease implicates direct ammonia consumption in the gut.

Probabilistic neural networks modeling of the 48-h LC50 acute toxicity endpoint to Daphnia magna.

PubMed

Niculescu, S P; Lewis, M A; Tigner, J

2008-01-01

Two modeling experiments based on the maximum likelihood estimation paradigm and targeting prediction of the Daphnia magna 48-h LC50 acute toxicity endpoint for both organic and inorganic compounds are reported. The resulting models computational algorithms are implemented as basic probabilistic neural networks with Gaussian kernel (statistical corrections included). The first experiment uses strictly D. magna information for 971 structures as training/learning data and the resulting model targets practical applications. The second experiment uses the same training/learning information plus additional data on another 29 compounds whose endpoint information is originating from D. pulex and Ceriodaphnia dubia. It only targets investigation of the effect of mixing strictly D. magna 48-h LC50 modeling information with small amounts of similar information estimated from related species, and this is done as part of the validation process. A complementary 81 compounds dataset (involving only strictly D. magna information) is used to perform external testing. On this external test set, the Gaussian character of the distribution of the residuals is confirmed for both models. This allows the use of traditional statistical methodology to implement computation of confidence intervals for the unknown measured values based on the models predictions. Examples are provided for the model targeting practical applications. For the same model, a comparison with other existing models targeting the same endpoint is performed.

Suspected acute coronary syndrome in the emergency room: Limited added value of heart type fatty acid binding protein point of care or ELISA tests: The FAME-ER (Fatty Acid binding protein in Myocardial infarction Evaluation in the Emergency Room) study.

PubMed

Bank, Ingrid Em; Dekker, Marieke S; Hoes, Arno W; Zuithoff, Nicolaas Pa; Verheggen, Peter Whm; de Vrey, Evelyn A; Wildbergh, Thierry X; Timmers, Leo; de Kleijn, Dominique Pv; Glatz, Jan Fc; Mosterd, Arend

2016-08-01

Timely recognition of acute coronary syndrome remains a challenge as many biomarkers, including troponin, remain negative in the first hours following the onset of chest pain. We assessed the diagnostic accuracy of heart-type fatty acid binding protein (H-FABP), a cardiac biomarker with potential value immediately post symptom onset. Prospective monocentre diagnostic accuracy study of H-FABP bedside point of care (CardioDetect®) and ELISA tests in acute coronary syndrome suspected patients presenting within 24 hours of symptom onset to the emergency department, in addition to clinical findings, electrocardiography and the currently recommended biomarker high sensitivity troponin-T (hs-cTnT). The final diagnosis of acute coronary syndrome was adjudicated by two independent cardiologists, blinded to H-FABP results. Acute coronary syndrome was diagnosed in 149 (32.9%) of 453 unselected patients with suspected acute coronary syndrome (56% men, mean age 62.6 years). Negative predictive values were similar for H-FABP point of care and ELISA tests (79% vs. 78% respectively), but inferior to initial hs-cTnT (negative predictive value 86%). The addition of H-FABP point of care results to hs-cTnT increased the negative predictive value to 89%. In a multivariable logistic regression model, H-FABP point of care and ELISA tests yielded relevant diagnostic information in addition to clinical findings and ECG (likelihood ratio test p<0.001) and increased area under the receiver operating characteristics curve (AUC; 0.82 vs. 0.84 and 0.84). This added value attenuated, however, after inclusion of hs-cTnT in the diagnostic model (AUC 0.88). In patients suspected of acute coronary syndrome presenting to the emergency department, H-FABP testing improves diagnostic accuracy in addition to clinical findings and electrocardiography. H-FABP, however, has no additional diagnostic value when hs-cTnT measurements are also available. © The European Society of Cardiology 2015.

Acute toxic nephropathies: clinical pathologic correlations.

PubMed

Muehrcke, R C; Volini, F I; Morris, A M; Moles, J B; Lawrence, A G

1976-01-01

Man's ever increasing exposure to numerous drugs and chemicals, which are the results of medical and industrial progress, produces a by-product of acute toxic nephropathies. These include acute toxic renal failure, drug-induced acute oliguric renal failure, acute hemorrhagic glomerulonephritis, nephrotic syndrome, tubular disturbances and potassium deficiency. In depth information is provided for the previously mentioned disorders.

Effect of acute pancreatitis on the pharmacokinetics of Chinese herbal ointment Liu-He-Dan in anaesthetized rats.

PubMed

Zhao, Xian-Lin; Xiang, Jin; Wan, Mei-Hua; Yu, Qin; Chen, Wei-wei; Chen, Guang-Yuan; Tang, Wen-Fu

2013-01-09

Chinese herbal preparation of Liu-He-Dan ointment has been adapted for acute pancreatitis in external application for many years in West China. To investigate the effect of acute pancreatitis on the pharmacokinetics of Liu-He-Dan ointment in rats while it was used externally on belly. Twelve male Sprague-Dawley rats were randomly divided into acute pancreatitis model group (n=6) and normal group as a control (n=6). Chinese herbal Liu-He-Dan ointment was used externally on belly. Emodin, rhein, aloe emodin, physcion and chrysophanol in plasma and pancreas (at 48 h) were detected and quantified by liquid chromatography-tandem mass spectrometry. Amylase in plasma were determined with iodide process. Among the five components, only emodin, aloe emodin and physcion from Liu-He-Dan were detected in plasma and pancreas. The absorption of each component was tended to decrease in acute pancreatitis group after topically management with Liu-He-Dan ointment on rats' abdomen. The T(max), C(max) and area under curve (AUC) of each component were distinctly lower in AP group than those in normal group (p<0.05). However, the T(1/2α) and mean retention time (MRT) of emodin lasted longer in acute pancreatitis group than those in normal group (p<0.05). There was no statistical difference in the MRT of aloe emodin and physcion between the two groups. Emodin could be detected in all rats' pancreas at 48 h in both groups, while its mean pancreatic concentration was higher in acute pancreatitis model group than in normal group (0.91 ± 0.68, 0.41 ± 0.36, respectively). Physcion could be detected in pancreas of most acute pancreatitis models, but not in normal rats. Aloe emodin was found in all pancreas from acute pancreatitis models while only one in normal group. The level of amylase in Liu-He-Dan group was obviously lower than that in the AP model group (p=0.0055). We concluded that acute pancreatitis may significantly affect the pharmacokinetics of Liu-He-Dan while external applied on belly, which indicated the dosage modification in AP. However, acute pancreatitis seems to promote the distribution of the detected components into pancreas. The ointment could help relieve the disease of pancreatitis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The network of Shanghai Stroke Service System (4S): A public health-care web-based database using automatic extraction of electronic medical records.

PubMed

Dong, Yi; Fang, Kun; Wang, Xin; Chen, Shengdi; Liu, Xueyuan; Zhao, Yuwu; Guan, Yangtai; Cai, Dingfang; Li, Gang; Liu, Jianmin; Liu, Jianren; Zhuang, Jianhua; Wang, Panshi; Chen, Xin; Shen, Haipeng; Wang, David Z; Xian, Ying; Feng, Wuwei; Campbell, Bruce Cv; Parsons, Mark; Dong, Qiang

2018-07-01

Background Several stroke outcome and quality control projects have demonstrated the success in stroke care quality improvement through structured process. However, Chinese health-care systems are challenged with its overwhelming numbers of patients, limited resources, and large regional disparities. Aim To improve quality of stroke care to address regional disparities through process improvement. Method and design The Shanghai Stroke Service System (4S) is established as a regional network for stroke care quality improvement in the Shanghai metropolitan area. The 4S registry uses a web-based database that automatically extracts data from structured electronic medical records. Site-specific education and training program will be designed and administrated according to their baseline characteristics. Both acute reperfusion therapies including thrombectomy and thrombolysis in the acute phase and subsequent care were measured and monitored with feedback. Primary outcome is to evaluate the differences in quality metrics between baseline characteristics (including rate of thrombolysis in acute stroke and key performance indicators in secondary prevention) and post-intervention. Conclusions The 4S system is a regional stroke network that monitors the ongoing stroke care quality in Shanghai. This project will provide the opportunity to evaluate the spectrum of acute stroke care and design quality improvement processes for better stroke care. A regional stroke network model for quality improvement will be explored and might be expanded to other large cities in China. Clinical Trial Registration-URL http://www.clinicaltrials.gov . Unique identifier: NCT02735226.

Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis.

PubMed

Ditre, Joseph W; Heckman, Bryan W; Zale, Emily L; Kosiba, Jesse D; Maisto, Stephen A

2016-07-01

Although animal models have consistently demonstrated acute pain inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsycINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Meta-analytic integration for both threshold and tolerance outcomes revealed that nicotine administered through tobacco smoke and other delivery systems (eg, patch, nasal spray) produced acute analgesic effects that may be characterized as small to medium in magnitude (Hedges g = 0.35, 95% confidence interval = 0.21-0.50). Publication bias-corrected estimates remained significant and indicated that these effects may be closer to small. Sex composition was observed to be a significant moderator, such that pain threshold effects were more robust among samples that included more men than women. These results help to clarify a mixed literature and may ultimately help to inform the treatment of both pain and nicotine dependence. Pain and tobacco smoking are both highly prevalent and comorbid conditions. Current smoking has been associated with more severe chronic pain and physical impairment. Acute nicotine-induced analgesia could make smoking more rewarding and harder to give up. Future research should use dynamic measures of experimental pain reactivity and further explore biopsychosocial mechanisms of action.

Comparison of fluid types for resuscitation after acute blood loss in mallard ducks (Anas platyrhynchos).

PubMed

Lichtenberger, Marla; Orcutt, Connie; Cray, Carolyn; Thamm, Douglas H; DeBehnke, Daniel; Page, Cheryl; Mull, Lori; Kirby, Rebecca

2009-10-01

The purpose of this study was to determine the LD(50) for acute blood loss in mallard ducks (Anas platyrhynchos), compare the mortality rate among 3 fluid resuscitation groups, and determine the time required for a regenerative RBC response. Prospective study. Medical College of Wisconsin Research facility. Eighteen mallard ducks were included for the LD(50) study and 28 for the fluid resuscitation study. Phlebotomy was performed during both the LD(50) and fluid resuscitation studies. Ducks in the fluid resuscitation study received a 5 mL/kg intravenous bolus of crystalloids, hetastarch (HES), or a hemoglobin-based oxygen-carrying solution (HBOCS). The LD(50) for acute blood loss was 60% of total blood volume. This blood volume was removed in the fluid resuscitation study to create a model of acute blood loss. Following fluid administration, 6 birds in the crystalloid group (66%), 4 birds in the HES group (40%), and 2 birds in the HBOCS group (20%) died. No statistical difference in mortality rate was seen among the 3 fluid resuscitation groups. Relative polychromasia evaluated post-phlebotomy demonstrated regeneration starting at 24 hours and continuing through 48 hours. The LD(50) for acute blood loss in mallard ducks was 60% of their total blood volume. Although no statistical difference in mortality rate was appreciated among the 3 fluid resuscitation groups, a trend of decreased mortality rate was observed in the HBOCS group. An early regenerative response was apparent following acute blood loss.

Consensus Modeling of Oral Rat Acute Toxicity

EPA Science Inventory

An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

PubMed Central

McCullough, Emily H.; Niyonkuru, Christian; Ozawa, Haishin; Loucks, Tammy L.; Dobos, Julie A.; Brett, Christopher A.; Santarsieri, Martina; Dixon, C. Edward; Berga, Sarah L.; Fabio, Anthony

2011-01-01

Abstract Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for both men and women. These findings represent a paradigm shift when thinking about the role of sex steroids in neuroprotection clinically after TBI. PMID:21488721

The cost effectiveness of licensed oromucosal midazolam (Buccolam(®)) for the treatment of children experiencing acute epileptic seizures: an approach when trial evidence is limited.

PubMed

Lee, Dawn; Gladwell, Daniel; Batty, Anthony J; Brereton, Nic; Tate, Elaine

2013-04-01

In the UK, two treatment options are used for acute epileptic seizures in the community-rectal diazepam and unlicensed buccal midazolam. In practice, the former is rarely used, with unlicensed buccal midazolam being widely recommended and prescribed by physicians. In September 2011, Buccolam(®) (licensed midazolam oromucosal solution) became the first medicine to receive a Paediatric-Use Marketing Authorization (PUMA) and it is indicated for the treatment of prolonged, acute, convulsive seizures by caregivers in the community for children (aged 6 months to <18 years) diagnosed with epilepsy. The approval process for a PUMA product differs from other marketing authorization processes and may be based upon small population subsets and may not, in some cases, require new safety or efficacy data to be generated; a similar situation to that seen for orphan drugs. This can lead to challenges when conducting economic evaluations. The aim of this study was to assess the cost effectiveness of Buccolam(®) for children with a diagnosis of epilepsy suffering prolonged, acute, convulsive seizures occurring in the UK community setting. DESIGN AND PERSPECTIVE: A hybrid model was developed according to a UK payer perspective. The model included a time-to-event simulation for the frequency and location of occurrence of seizures, along with a decision-tree model that assessed the treatment pathway when a seizure occured. The model compared treatment with Buccolam(®) with standard care in the community (95 % unlicensed buccal midazolam and 5 % rectal diazepam) or either treatment alone. The model was informed by data from a variety of sources, including clinical effectiveness estimates, and costs based on published UK data, using 2012-13 prices, where possible. To determine current practice and real-world effectiveness, a Delphi panel and a survey of parents of children with epilepsy were conducted. Buccolam(®) showed a reduction in costs of £2,939 compared with standard care, £14,269 compared with rectal diazepam alone and £886 compared with unlicensed buccal midazolam alone. Increases of 0.025, 0.082 and 0.013 quality-adjusted life-years, respectively, were also seen. Buccolam(®) remained dominant across a range of scenario analyses. This model demonstrates the possibility of constructing a thorough economic case when trial or real-world data are not available. The results of the model show Buccolam(®) to be cost saving compared with rectal diazepam due to a reduction in the need for ambulance callouts and hospital stays, and compared with unlicensed buccal midazolam, through reduced drug costs and wastage.

Development of algal interspecies correlation estimation models for chemical hazard assessment.

PubMed

Brill, Jessica L; Belanger, Scott E; Chaney, Joel G; Dyer, Scott D; Raimondo, Sandy; Barron, Mace G; Pittinger, Charles A

2016-09-01

Web-based Interspecies Correlation Estimation (ICE) is an application developed to predict the acute toxicity of a chemical from 1 species to another taxon. Web-ICE models use the acute toxicity value for a surrogate species to predict effect values for other species, thus potentially filling in data gaps for a variety of environmental assessment purposes. Web-ICE has historically been dominated by aquatic and terrestrial animal prediction models. Web-ICE models for algal species were essentially absent and are addressed in the present study. A compilation of public and private sector-held algal toxicity data were compiled and reviewed for quality based on relevant aspects of individual studies. Interspecies correlations were constructed from the most commonly tested algal genera for a broad spectrum of chemicals. The ICE regressions were developed based on acute 72-h and 96-h endpoint values involving 1647 unique studies on 476 unique chemicals encompassing 40 genera and 70 species of green, blue-green, and diatom algae. Acceptance criteria for algal ICE models were established prior to evaluation of individual models and included a minimum sample size of 3, a statistically significant regression slope, and a slope estimation parameter ≥0.65. A total of 186 ICE models were possible at the genus level, with 21 meeting quality criteria; and 264 ICE models were developed at the species level, with 32 meeting quality criteria. Algal ICE models will have broad utility in screening environmental hazard assessments, data gap filling in certain regulatory scenarios, and as supplemental information to derive species sensitivity distributions. Environ Toxicol Chem 2016;35:2368-2378. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

The derivation and validation of a simple model for predicting in-hospital mortality of acutely admitted patients to internal medicine wards.

PubMed

Sakhnini, Ali; Saliba, Walid; Schwartz, Naama; Bisharat, Naiel

2017-06-01

Limited information is available about clinical predictors of in-hospital mortality in acute unselected medical admissions. Such information could assist medical decision-making.To develop a clinical model for predicting in-hospital mortality in unselected acute medical admissions and to test the impact of secondary conditions on hospital mortality.This is an analysis of the medical records of patients admitted to internal medicine wards at one university-affiliated hospital. Data obtained from the years 2013 to 2014 were used as a derivation dataset for creating a prediction model, while data from 2015 was used as a validation dataset to test the performance of the model. For each admission, a set of clinical and epidemiological variables was obtained. The main diagnosis at hospitalization was recorded, and all additional or secondary conditions that coexisted at hospital admission or that developed during hospital stay were considered secondary conditions.The derivation and validation datasets included 7268 and 7843 patients, respectively. The in-hospital mortality rate averaged 7.2%. The following variables entered the final model; age, body mass index, mean arterial pressure on admission, prior admission within 3 months, background morbidity of heart failure and active malignancy, and chronic use of statins and antiplatelet agents. The c-statistic (ROC-AUC) of the prediction model was 80.5% without adjustment for main or secondary conditions, 84.5%, with adjustment for the main diagnosis, and 89.5% with adjustment for the main diagnosis and secondary conditions. The accuracy of the predictive model reached 81% on the validation dataset.A prediction model based on clinical data with adjustment for secondary conditions exhibited a high degree of prediction accuracy. We provide a proof of concept that there is an added value for incorporating secondary conditions while predicting probabilities of in-hospital mortality. Further improvement of the model performance and validation in other cohorts are needed to aid hospitalists in predicting health outcomes.

Cardiovascular Events Following Smoke-Free Legislations: An Updated Systematic Review and Meta-Analysis

PubMed Central

Jones, Miranda R.; Barnoya, Joaquin; Stranges, Saverio; Losonczy, Lia; Navas-Acien, Ana

2014-01-01

Background Legislations banning smoking in indoor public places and workplaces are being implemented worldwide to protect the population from secondhand smoke exposure. Several studies have reported reductions in hospitalizations for acute coronary events following the enactment of smoke-free laws. Objective We set out to conduct a systematic review and meta-analysis of epidemiologic studies examining how legislations that ban smoking in indoor public places impact the risk of acute coronary events. Methods We searched MEDLINE, EMBASE, and relevant bibliographies including previous systematic reviews for studies that evaluated changes in acute coronary events, following implementation of smoke-free legislations. Studies were identified through December 2013. We pooled relative risk (RR) estimates for acute coronary events comparing post- vs. pre-legislation using inverse-variance weighted random-effects models. Results Thirty-one studies providing estimates for 47 locations were included. The legislations were implemented between 1991 and 2010. Following the enactment of smoke-free legislations, there was a 12 % reduction in hospitalizations for acute coronary events (pooled RR: 0.88, 95 % CI: 0.85–0.90). Reductions were 14 % in locations that implemented comprehensive legislations compared to an 8 % reduction in locations that only had partial restrictions. In locations with reductions in smoking prevalence post-legislation above the mean (2.1 % reduction) there was a 14 % reduction in events compared to 10 % in locations below the mean. The RRs for acute coronary events associated with enacting smoke-free legislation were 0.87 vs. 0.89 in locations with smoking prevalence pre-legislation above and below the mean (23.1 %), and 0.87 vs. 0.89 in studies from the Americas vs. other regions. Conclusion The implementation of smoke-free legislations was related to reductions in acute coronary event hospitalizations in most populations evaluated. Benefits are greater in locations with comprehensive legislations and with greater reduction in smoking prevalence post-legislation. These cardiovascular benefits reinforce the urgent need to enact and enforce smoke-free legislations that protect all citizens around the world from exposure to tobacco smoke in public places. PMID:25328861

Prevalence of factors associated with malnutrition among acute geriatric patients in Norway: a cross-sectional study

PubMed Central

Jacobsen, Ellisiv Lærum; Brovold, Therese; Bergland, Astrid; Bye, Asta

2016-01-01

Objectives Data on acute geriatric patients' nutritional status are lacking, and the associations among physical function, sarcopenia, health status and nutritional status are not sufficiently investigated in this population. The aims of this study are to investigate (1) nutritional status and sarcopenia in a group of acute geriatric patients, (2) the association between nutritional status, physical function and sarcopenia in acute geriatric patients, controlling for health status. Design A cross-sectional study. Setting Two acute geriatric hospital wards in Norway. Participants This study included 120 patients with a mean age of 82.6±8 years. The following inclusion criteria were used: age ≥65 years and admitted to an acute geriatric ward. The exclusion criteria included terminal illness, Mini-Mental State Examination <23, language difficulties or severe aphasia. Main outcome measures Nutritional status was assessed using the Mini Nutritional Assessment (MNA). Physical function was measured using the Barthel activities of daily life index and the Short Physical Performance Battery (SPPB). Sarcopenia was diagnosed using the mid-arm muscle circumference, gait speed and grip strength, in accordance with the EWGSOP algorithm. Diseases are organised by organ system classification. Results On the basis of the MNA classification, nearly one in two patients were at risk of malnutrition, while one in four were malnourished. Sarcopenia was present in 30% of the patients. A multivariate linear regression model was estimated and showed significant independent associations between SPPB score (β 0.64, 95% CI 0.38 to 0.90), sarcopenia (β −3.3, 95% CI −4.9 to −1.7), pulmonary disease (β −2.1, 95% CI −3.7 to −0.46), cancer (β −1.7, 95% CI −3.4 to −0.033) and nutritional status. Conclusions Our study shows a high prevalence of risk of malnutrition, malnutrition and sarcopenia. Further, the results indicate that a low total SPPB score, sarcopenia, cancer and pulmonary disease are significantly associated with declines in nutritional status, as measured by the MNA, in acute geriatric patients. PMID:27601491

Prevalence of factors associated with malnutrition among acute geriatric patients in Norway: a cross-sectional study.

PubMed

Jacobsen, Ellisiv Lærum; Brovold, Therese; Bergland, Astrid; Bye, Asta

2016-09-06

Data on acute geriatric patients' nutritional status are lacking, and the associations among physical function, sarcopenia, health status and nutritional status are not sufficiently investigated in this population. The aims of this study are to investigate (1) nutritional status and sarcopenia in a group of acute geriatric patients, (2) the association between nutritional status, physical function and sarcopenia in acute geriatric patients, controlling for health status. A cross-sectional study. Two acute geriatric hospital wards in Norway. This study included 120 patients with a mean age of 82.6±8 years. The following inclusion criteria were used: age ≥65 years and admitted to an acute geriatric ward. The exclusion criteria included terminal illness, Mini-Mental State Examination <23, language difficulties or severe aphasia. Nutritional status was assessed using the Mini Nutritional Assessment (MNA). Physical function was measured using the Barthel activities of daily life index and the Short Physical Performance Battery (SPPB). Sarcopenia was diagnosed using the mid-arm muscle circumference, gait speed and grip strength, in accordance with the EWGSOP algorithm. Diseases are organised by organ system classification. On the basis of the MNA classification, nearly one in two patients were at risk of malnutrition, while one in four were malnourished. Sarcopenia was present in 30% of the patients. A multivariate linear regression model was estimated and showed significant independent associations between SPPB score (β 0.64, 95% CI 0.38 to 0.90), sarcopenia (β -3.3, 95% CI -4.9 to -1.7), pulmonary disease (β -2.1, 95% CI -3.7 to -0.46), cancer (β -1.7, 95% CI -3.4 to -0.033) and nutritional status. Our study shows a high prevalence of risk of malnutrition, malnutrition and sarcopenia. Further, the results indicate that a low total SPPB score, sarcopenia, cancer and pulmonary disease are significantly associated with declines in nutritional status, as measured by the MNA, in acute geriatric patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Transgenic Mice with Increased Astrocyte Expression of IL-6 Show Altered Effects of Acute Ethanol on Synaptic Function

PubMed Central

Hernandez, Ruben V.; Puro, Alana C.; Manos, Jessica C.; Huitron-Resendiz, Salvador; Reyes, Kenneth C.; Liu, Kevin; Vo, Khanh; Roberts, Amanda J.; Gruol, Donna L.

2015-01-01

A growing body of evidence has revealed that resident cells of the central nervous system (CNS), and particularly the glial cells, comprise a neuroimmune system that serves a number of functions in the normal CNS and during adverse conditions. Cells of the neuroimmune system regulate CNS functions through the production of signaling factors, referred to as neuroimmune factors. Recent studies show that ethanol can activate cells of the neuroimmune system, resulting in the elevated production of neuroimmune factors, including the cytokine interleukin-6 (IL-6). Here we analyzed the consequences of this CNS action of ethanol using transgenic mice that express elevated levels of IL-6 through increased astrocyte expression (IL-6-tg) to model the increased IL-6 expression that occurs with ethanol use. Results show that increased IL-6 expression induces neuroadaptive changes that alter the effects of ethanol. In hippocampal slices from non-transgenic (non-tg) littermate control mice, synaptically evoked dendritic field excitatory postsynaptic potential (fEPSP) and somatic population spike (PS) at the Schaffer collateral to CA1 pyramidal neuron synapse were reduced by acute ethanol (20 or 60 mM). In contrast, acute ethanol enhanced the fEPSP and PS in hippocampal slices from IL-6 tg mice. Long-term synaptic plasticity of the fEPSP (i.e., LTP) showed the expected dose-dependent reduction by acute ethanol in non-tg hippocampal slices, whereas LTP in the IL-6 tg hippocampal slices was resistant to this depressive effect of acute ethanol. Consistent with altered effects of acute ethanol on synaptic function in the IL-6 tg mice, EEG recordings showed a higher level of CNS activity in the IL-6 tg mice than in the non-tg mice during the period of withdrawal from an acute high dose of ethanol. These results suggest a potential role for neuroadaptive effects of ethanol-induced astrocyte production of IL-6 as a mediator or modulator of the actions of ethanol on the CNS, including persistent changes in CNS function that contribute to cognitive dysfunction and the development of alcohol dependence. PMID:26707655

Methodological considerations, such as directed acyclic graphs, for studying "acute on chronic" disease epidemiology: chronic obstructive pulmonary disease example.

PubMed

Tsai, Chu-Lin; Camargo, Carlos A

2009-09-01

Acute exacerbations of chronic disease are ubiquitous in clinical medicine, and thus far, there has been a paucity of integrated methodological discussion on this phenomenon. We use acute exacerbations of chronic obstructive pulmonary disease as an example to emphasize key epidemiological and statistical issues for this understudied field in clinical epidemiology. Directed acyclic graphs are a useful epidemiological tool to explain the differential effects of risk factor on health outcomes in studies of acute and chronic phases of disease. To study the pathogenesis of acute exacerbations of chronic disease, case-crossover design and time-series analysis are well-suited study designs to differentiate acute and chronic effect. Modeling changes over time and setting appropriate thresholds are important steps to separate acute from chronic phases of disease in serial measurements. In statistical analysis, acute exacerbations are recurrent events, and some individuals are more prone to recurrences than others. Therefore, appropriate statistical modeling should take into account intraindividual dependence. Finally, we recommend the use of "event-based" number needed to treat (NNT) to prevent a single exacerbation instead of traditional patient-based NNT. Addressing these methodological challenges will advance research quality in acute on chronic disease epidemiology.

Young Children's Acute Stress After a Burn Injury: Disentangling the Role of Injury Severity and Parental Acute Stress.

PubMed

Haag, Ann-Christin; Landolt, Markus A

2017-09-01

Although injury severity and parental stress are strong predictors of posttraumatic adjustment in young children after burns, little is known about the interplay of these variables. This study aimed at clarifying mediation processes between injury severity and mother's, father's, and young child's acute stress. Structural equation modeling was used to examine the relationships between injury severity and parental and child acute stress. Parents of 138 burn-injured children (ages 1-4 years) completed standardized questionnaires on average 19 days postinjury. Sixteen children (11.7%) met Diagnostic and Statistical Manual of Mental Disorders, 5th edition, preschool criteria for posttraumatic stress disorder (excluding time criterion). The model revealed a significant mediation of maternal acute stress, with the effect of injury severity on a child's acute stress mediated by maternal acute stress. Paternal acute stress failed to serve as a mediating variable. Our findings confirm mothers' crucial role in the posttraumatic adjustment of young children. Clinically, mothers' acute stress should be monitored. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

A re-evaluation of PETROTOX for predicting acute and chronic toxicity of petroleum substances.

PubMed

Redman, Aaron D; Parkerton, Thomas F; Leon Paumen, Miriam; Butler, Josh D; Letinski, Daniel J; den Haan, Klass

2017-08-01

The PETROTOX model was developed to perform aquatic hazard assessment of petroleum substances based on substance composition. The model relies on the hydrocarbon block method, which is widely used for conducting petroleum substance risk assessments providing further justification for evaluating model performance. Previous work described this model and provided a preliminary calibration and validation using acute toxicity data for limited petroleum substance. The objective of the present study was to re-evaluate PETROTOX using expanded data covering both acute and chronic toxicity endpoints on invertebrates, algae, and fish for a wider range of petroleum substances. The results indicated that recalibration of 2 model parameters was required, namely, the algal critical target lipid body burden and the log octanol-water partition coefficient (K OW ) limit, used to account for reduced bioavailability of hydrophobic constituents. Acute predictions from the updated model were compared with observed toxicity data and found to generally be within a factor of 3 for algae and invertebrates but overestimated fish toxicity. Chronic predictions were generally within a factor of 5 of empirical data. Furthermore, PETROTOX predicted acute and chronic hazard classifications that were consistent or conservative in 93 and 84% of comparisons, respectively. The PETROTOX model is considered suitable for the purpose of characterizing petroleum substance hazard in substance classification and risk assessments. Environ Toxicol Chem 2017;36:2245-2252. © 2017 SETAC. © 2017 SETAC.

Predictors of Acute Bacterial Meningitis in Children from a Malaria-Endemic Area of Papua New Guinea

PubMed Central

Laman, Moses; Manning, Laurens; Greenhill, Andrew R.; Mare, Trevor; Michael, Audrey; Shem, Silas; Vince, John; Lagani, William; Hwaiwhanje, Ilomo; Siba, Peter M.; Mueller, Ivo; Davis, Timothy M. E.

2012-01-01

Predictors of acute bacterial meningitis (ABM) were assessed in 554 children in Papua New Guinea 0.2–10 years of age who were hospitalized with culture-proven meningitis, probable meningitis, or non-meningitic illness investigated by lumbar puncture. Forty-seven (8.5%) had proven meningitis and 36 (6.5%) had probable meningitis. Neck stiffness, Kernig’s and Brudzinski’s signs and, in children < 18 months of age, a bulging fontanel had positive likelihood ratios (LRs) ≥ 4.3 for proven/probable ABM. Multiple seizures and deep coma were less predictive (LR = 1.5–2.1). Single seizures and malaria parasitemia had low LRs (≤ 0.5). In logistic regression including clinical variables, Kernig’s sign and deep coma were positively associated with ABM, and a single seizure was negatively associated (P ≤ 0.01). In models including microscopy, neck stiffness and deep coma were positively associated with ABM and parasitemia was negatively associated with ABM (P ≤ 0.04). In young children, a bulging fontanel added to the model (P < 0.001). Simple clinical features predict ABM in children in Papua New Guinea but malaria microscopy augments diagnostic precision. PMID:22302856

Herpes Simplex Virus 1 Infection of Tree Shrews Differs from That of Mice in the Severity of Acute Infection and Viral Transcription in the Peripheral Nervous System

PubMed Central

Li, Lihong; Li, Zhuoran; Wang, Erlin; Yang, Rui; Xiao, Yu; Han, Hongbo; Lang, Fengchao; Li, Xin; Xia, Yujie; Gao, Feng; Li, Qihan; Fraser, Nigel W.

2015-01-01

ABSTRACT Studies of herpes simplex virus (HSV) infections of humans are limited by the use of rodent models such as mice, rabbits, and guinea pigs. Tree shrews (Tupaia belangeri chinensis) are small mammals indigenous to southwest Asia. At behavioral, anatomical, genomic, and evolutionary levels, tree shrews are much closer to primates than rodents are, and tree shrews are susceptible to HSV infection. Thus, we have studied herpes simplex virus 1 (HSV-1) infection in the tree shrew trigeminal ganglion (TG) following ocular inoculation. In situ hybridization, PCR, and quantitative reverse transcription-PCR (qRT-PCR) analyses confirm that HSV-1 latently infects neurons of the TG. When explant cocultivation of trigeminal ganglia was performed, the virus was recovered after 5 days of cocultivation with high efficiency. Swabbing the corneas of latently infected tree shrews revealed that tree shrews shed virus spontaneously at low frequencies. However, tree shrews differ significantly from mice in the expression of key HSV-1 genes, including ICP0, ICP4, and latency-associated transcript (LAT). In acutely infected tree shrew TGs, no level of ICP4 was observed, suggesting the absence of infection or a very weak, acute infection compared to that of the mouse. Immunofluorescence staining with ICP4 monoclonal antibody, and immunohistochemistry detection by HSV-1 polyclonal antibodies, showed a lack of viral proteins in tree shrew TGs during both acute and latent phases of infection. Cultivation of supernatant from homogenized, acutely infected TGs with RS1 cells also exhibited an absence of infectious HSV-1 from tree shrew TGs. We conclude that the tree shrew has an undetectable, or a much weaker, acute infection in the TGs. Interestingly, compared to mice, tree shrew TGs express high levels of ICP0 transcript in addition to LAT during latency. However, the ICP0 transcript remained nuclear, and no ICP0 protein could be seen during the course of mouse and tree shrew TG infections. Taken together, these observations suggest that the tree shrew TG infection differs significantly from the existing rodent models. IMPORTANCE Herpes simplex viruses (HSVs) establish lifelong infection in more than 80% of the human population, and their reactivation leads to oral and genital herpes. Currently, rodent models are the preferred models for latency studies. Rodents are distant from primates and may not fully represent human latency. The tree shrew is a small mammal, a prosimian primate, indigenous to southwest Asia. In an attempt to further develop the tree shrew as a useful model to study herpesvirus infection, we studied the establishment of latency and reactivation of HSV-1 in tree shrews following ocular inoculation. We found that the latent virus, which resides in the sensory neurons of the trigeminal ganglion, could be stress reactivated to produce infectious virus, following explant cocultivation and that spontaneous reactivation could be detected by cell culture of tears. Interestingly, the tree shrew model is quite different from the mouse model of HSV infection, in that the virus exhibited only a mild acute infection following inoculation with no detectable infectious virus from the sensory neurons. The mild infection may be more similar to human infection in that the sensory neurons continue to function after herpes reactivation and the affected skin tissue does not lose sensation. Our findings suggest that the tree shrew is a viable model to study HSV latency. PMID:26512084

Zebrafish (Danio rerio) Models To Assess Acute, Developmental, And Neurodevelopmental Toxicity

EPA Science Inventory

Zebrafish (Danio rerio) acute, developmental, and neurodevelopmental model systems have been developed to assess both known and unknown environmental contaminants. Developmental toxicity is assessed using death and dysmorphology as endpoints, whereas neurodevelopmental toxicity ...

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

PubMed Central

Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

PubMed

Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.

PubMed

Fagherazzi, Elen V; Garcia, Vanessa A; Maurmann, Natasha; Bervanger, Thielly; Halmenschlager, Luis H; Busato, Stefano B; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Schröder, Nadja

2012-02-01

Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies. Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases. We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats. Rats received vehicle or iron at postnatal days 12-14. At the age of 2 months, they received an acute intraperitoneal injection of vehicle or cannabidiol (5.0 or 10.0 mg/kg) immediately after the training session of the novel object recognition task. In order to investigate the effects of chronic cannabidiol, iron-treated rats received daily intraperitoneal injections of cannabidiol for 14 days. Twenty-four hours after the last injection, they were submitted to object recognition training. Retention tests were performed 24 h after training. A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats. The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders. Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.

Evidence for host genetic regulation of altered lipid metabolism in experimental toxoplasmosis supported with gene data mining results

PubMed Central

2017-01-01

Toxoplasma gondii is one of the most successful parasites on Earth, infecting a wide array of mammals including one third of the global human population. The obligate intracellular protozoon is not capable of synthesizing cholesterol (Chl), and thus depends on uptake of host Chl for its own development. To explore the genetic regulation of previously observed lipid metabolism alterations during acute murine T. gondii infection, we here assessed total Chl and its fractions in serum and selected tissues at the pathophysiological and molecular level, and integrated the observed gene expression of selected molecules relevant for Chl metabolism, including its biosynthetic and export KEGG pathways, with the results of published transcriptomes obtained in similar murine models of T. gondii infection. The serum lipid status as well as the transcript levels of relevant genes in the brain and the liver were assessed in experimental models of acute and chronic toxoplasmosis in wild-type mice. The results showed that acute infection was associated with a decrease in Chl content in both the liver and periphery (brain, peripheral lymphocytes), and a decrease in Chl reverse transport. In contrast, in chronic infection, a return to normal levels of Chl metabolism has been noted. These changes corresponded to the brain and liver gene expression results as well as to data obtained via mining. We propose that the observed changes in Chl metabolism are part of the host defense response. Further insight into the lipid metabolism in T. gondii infection may provide novel targets for therapeutic agents. PMID:28459857

Protective Effect of Thalidomide on Liver Injury in Rats with Acute Pancreatitis via Inhibition of Oxidative Stress.

PubMed

Lv, Peng; Fan, Li-Juan; Li, Hong-Yun; Meng, Qing-Shun; Liu, Jie

2015-01-01

This study was designed to investigate the preventive effect of thalidomide on acute pancreatitis-associated liver injury in the rat and analyze its relationship with oxidative stress. The acute pancreatitis of rats was induced by the retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Thalidomide (100 mg/kg) was given daily via the intragastric route for 8 days before this injection. The levels of oxidative stress parameters including superoxide dismutase (SOD), glutathione peroxidase (GSHpx), and malondialdehyde (MDA) in the liver were detected by biochemical assay. Nuclear factor-κB p65 (NF-κBp65), tumor necrosis factor α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) protein and mRNA levels in the liver were detected using western blots and reverse transcriptase polymerase chain reaction, respectively. Compared with the untreated model group, liver histopathology, SOD, GSHpx, MDA levels, NF-κBp65, TNF-α, ICAM-1 protein, and mRNA levels in the liver of rats given thalidomide were improved significantly. Results demonstrate that thalidomide may exert its effects on oxidative stress to attenuate the progression of acute pancreatitis-associated liver injury in rats. © 2015 by the Association of Clinical Scientists, Inc.

Adult Acute Myeloid Leukemia Treatment (PDQ®)—Health Professional Version

Cancer.gov

Acute myeloid leukemia (AML; also called acute myelogenous leukemia, acute nonlymphocytic leukemia) treatment advances have resulted in substantially improved CR rates. Cytogenetic analysis helps predict outcomes of treatment which includes chemotherapy, radiation, and stem cell transplant. Get detailed information about AML in this clinician summary.

A hyperacute neurology team - transforming emergency neurological care.

PubMed

Nitkunan, Arani; MacDonald, Bridget K; Boodhoo, Ajay; Tomkins, Andrew; Smyth, Caitlin; Southam, Medina; Schon, Fred

2017-07-01

We present the results of an 18-month study of a new model of how to care for emergency neurological admissions. We have established a hyperacute neurology team at a single district general hospital. Key features are a senior acute neurology nurse coordinator, an exclusively consultant-delivered service, acute epilepsy nurses, an acute neurophysiology service supported by neuroradiology and acute physicians and based within the acute medical admissions unit. Key improvements are a major increase in the number of patients seen, the speed with which they are seen and the percentage seen on acute medical unit before going to the general wards. We have shown a reduced length of stay and readmission rates for patients with epilepsy. Epilepsy accounted for 30% of all referrals. The cost implications of running this service are modest. We feel that this model is worthy of widespread consideration. © Royal College of Physicians 2017. All rights reserved.

Severe acute respiratory syndrome (SARS)

MedlinePlus

SARS; Respiratory failure - SARS ... Complications may include: Respiratory failure Liver failure Heart failure ... 366. McIntosh K, Perlman S. Coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). ...

Primary Sjogren's syndrome and the risk of acute pancreatitis: a nationwide cohort study.

PubMed

Chang, Chi-Ching; Chang, Yu-Sheng; Wang, Shu-Hung; Lin, Shyr-Yi; Chen, Yi-Hsuan; Chen, Jin Hua

2017-08-11

Studies on the risk of acute pancreatitis in patients with primary Sjogren's syndrome (pSS) are limited. We evaluated the effects of pSS on the risk of acute pancreatitis in a nationwide, population-based cohort in Taiwan. Population-based retrospective cohort study. We studied the claims data of the >97% Taiwan population from 2002 to 2012. We identified 9468 patients with pSS by using the catastrophic illness registry of the National Health Insurance Database in Taiwan. We also selected 37 872 controls that were randomly frequency matched by age (in 5 year bands), sex and index year from the general population. We analysed the risk of acute pancreatitis by using Cox proportional hazards regression models including sex, age and comorbidities. From 23.74 million people in the cohort, 9468 patients with pSS (87% women, mean age=55.6 years) and 37 872 controls were followed-up for 4.64 and 4.74 years, respectively. A total of 44 cases of acute pancreatitis were identified in the pSS cohort versus 105 cases in the non-pSS cohort. Multivariate Cox regression analysis indicated that the incidence rate of acute pancreatitis was significantly higher in the pSS cohort than in the non-pSS cohort (adjusted HR (aHR) 1.48, 95% CI 1.03 to 2.12). Cyclophosphamide use increased the risk of acute pancreatitis (aHR 5.27, 95% CI 1.16 to 23.86). By contrast, hydroxychloroquine reduced the risk of acute pancreatitis (aHR 0.23, 95% CI 0.09 to 0.55). This nationwide, retrospective cohort study demonstrated that the risk of acute pancreatitis was significantly higher in patients with pSS than in the general population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prognostic nomogram for previously untreated adult patients with acute myeloid leukemia

PubMed Central

Zheng, Zhuojun; Li, Xiaodong; Zhu, Yuandong; Gu, Weiying; Xie, Xiaobao; Jiang, Jingting

2016-01-01

This study was designed to perform an acceptable prognostic nomogram for acute myeloid leukemia. The clinical data from 311 patients from our institution and 165 patients generated with Cancer Genome Atlas Research Network were reviewed. A prognostic nomogram was designed according to the Cox's proportional hazard model to predict overall survival (OS). To compare the capacity of the nomogram with that of the current prognostic system, the concordance index (C-index) was used to validate the accuracy as well as the calibration curve. The nomogram included 6 valuable variables: age, risk stratifications based on cytogenetic abnormalities, status of FLT3-ITD mutation, status of NPM1 mutation, expression of CD34, and expression of HLA-DR. The C-indexes were 0.71 and 0.68 in the primary and validation cohort respectively, which were superior to the predictive capacity of the current prognostic systems in both cohorts. The nomogram allowed both patients with acute myeloid leukemia and physicians to make prediction of OS individually prior to treatment. PMID:27689396

Trends in acute mental health care: comparing psychiatric and substance abuse treatment programs.

PubMed

Timko, Christine; Lesar, Michelle; Calvi, Noël J; Moos, Rudolf H

2003-01-01

This study compared psychiatric and substance abuse acute care programs, within both inpatient and residential modalities of care, on organization and staffing, clinical management practices and policies, and services and activities. A total of 412 (95% of those eligible) Department of Veterans Affairs' programs were surveyed nationwide. Some 40% to 50% of patients in psychiatric and substance abuse programs, in both inpatient and residential venues of care, had dual diagnoses. Even though psychiatric programs had a sicker patient population, they provided fewer services, including basic components of integrated programs, than substance abuse programs did. Findings also showed that there is a strong emphasis on the use of clinical practice guidelines, performance monitoring, and obtaining client satisfaction and outcome data in mental health programs. The author's suggest how psychiatric programs might better meet the needs of acutely ill and dually diagnosed patients (e.g., by incorporating former patients as role models and mutual help groups, as substance abuse programs do; and by having policies that balance patient choice with program demand).

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model

PubMed Central

Jackson, George R.; Maione, Anna G.; Klausner, Mitchell

2018-01-01

Abstract Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal (in vitro) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1–2 and EPA Acute Inhalation Toxicity Category I–II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity. PMID:29904643

Administration of 2-arachidonoylglycerol ameliorates both acute and chronic experimental autoimmune encephalomyelitis.

PubMed

Lourbopoulos, Athanasios; Grigoriadis, Nikolaos; Lagoudaki, Roza; Touloumi, Olga; Polyzoidou, Eleni; Mavromatis, Ioannis; Tascos, Nikolaos; Breuer, Aviva; Ovadia, Haim; Karussis, Dimitris; Shohami, Ester; Mechoulam, Raphael; Simeonidou, Constantina

2011-05-16

Experimental autoimmune encephalomyelitis (EAE) is a widely used model of multiple sclerosis (MS) and both conditions have been reported to exhibit reduced endocannabinoid activity. The purpose of this study was to address the effect of exogenously administered 2-arachidonoylglycerol (2AG), an endocannabinoid receptor ligand, on acute phase and chronic disability in EAE. Acute and chronic EAE models were induced in susceptible mice and 2AG-treatment was applied for 14 days from day of disease induction. 2AG-treatment ameliorated acute phase of disease with delay of disease onset in both EAE models and reduced disease mortality and long-term (70 days post-induction) clinical disability in chronic EAE. Reduced axonal pathology in the chronic EAE- (p<0.0001) and increased activation and ramification of microglia in the 2AG-treated acute EAE- (p<0.05) model were noticed. The latter was accompanied by a 2- to 4-fold increase of the M2-macrophages in the perivascular infiltrations (p<0.001) of the 2AG-treated animals in the acute (day 22), although not the chronic (day 70), EAE model. Expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R) was increased in 2AG-treated animals of acute EAE vs. controls (p<0.05). In addition, ex vivo viability assays exhibited reduced proliferation of activated lymph node cells when extracted from 2AG-treated EAE animals, whereas a dose-dependent response of activated lymphocytes to 2AG-treatment in vitro was noticed. Our data indicate for the first time that 2AG treatment may provide direct (via CBRs) and immune (via M2 macrophages) mediated neuroprotection in EAE. Copyright © 2011 Elsevier B.V. All rights reserved.

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model.

PubMed

Jackson, George R; Maione, Anna G; Klausner, Mitchell; Hayden, Patrick J

2018-06-01

Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal ( in vitro ) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1-2 and EPA Acute Inhalation Toxicity Category I-II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity.

Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation

DTIC Science & Technology

2017-11-01

acute ) models of chemically-induced colitis. Based upon our studies, we believe the the rationale for the use of MSCs to treat patients with...rodent models of IBD, virtually all of these studies have used clinically-questionable doses of MSCs in 10 erosive, self-limiting (i.e. acute ...been demonstrated that ILC3-derived IL-22 attenuates acute and chronic intestinal inflam- mation induced in lymphopenic mice (Rag−/− mice) by Citrobacter

Derivation and Validation of a Risk Standardization Model for Benchmarking Hospital Performance for Health-Related Quality of Life Outcomes after Acute Myocardial Infarction

PubMed Central

Arnold, Suzanne V.; Masoudi, Frederick A.; Rumsfeld, John S.; Li, Yan; Jones, Philip G.; Spertus, John A.

2014-01-01

Background Before outcomes-based measures of quality can be used to compare and improve care, they must be risk-standardized to account for variations in patient characteristics. Despite the importance of health-related quality of life (HRQL) outcomes among patients with acute myocardial infarction (AMI), no risk-standardized models have been developed. Methods and Results We assessed disease-specific HRQL using the Seattle Angina Questionnaire at baseline and 1 year later in 2693 unselected AMI patients from 24 hospitals enrolled in the TRIUMPH registry. Using 57 candidate sociodemographic, economic, and clinical variables present on admission, we developed a parsimonious, hierarchical linear regression model to predict HRQL. Eleven variables were independently associated with poor HRQL after AMI, including younger age, prior CABG, depressive symptoms, and financial difficulties (R2=20%). The model demonstrated excellent internal calibration and reasonable calibration in an independent sample of 1890 AMI patients in a separate registry, although the model slightly over-predicted HRQL scores in the higher deciles. Among the 24 TRIUMPH hospitals, 1-year unadjusted HRQL scores ranged from 67–89. After risk-standardization, HRQL scores variability narrowed substantially (range=79–83), and the group of hospital performance (bottom 20%/middle 60%/top 20%) changed in 14 of the 24 hospitals (58% reclassification with risk-standardization). Conclusions In this predictive model for HRQL after AMI, we identified risk factors, including economic and psychological characteristics, associated with HRQL outcomes. Adjusting for these factors substantially altered the rankings of hospitals as compared with unadjusted comparisons. Using this model to compare risk-standardized HRQL outcomes across hospitals may identify processes of care that maximize this important patient-centered outcome. PMID:24163068

Establishment of a chronic activity-based anorexia rat model.

PubMed

Frintrop, Linda; Trinh, Stefanie; Liesbrock, Johanna; Paulukat, Lisa; Kas, Martien J; Tolba, Rene; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

2018-01-01

Anorexia nervosa (AN) is often a chronic eating disorder characterised by body image disturbance and low body weight often associated with starvation-induced amenorrhoea and excessive exercise. Activity-based anorexia (ABA) is an animal model representing many somatic aspects of this psychiatric illness. We systematically manipulated the extent and length of starvation and animal age to find the optimal parameters to study chronic starvation. Wistar rats had 24h/day running wheel access and received 40% of their baseline food intake until a 20% or 25% weight reduction was reached (acute starvation). This body weight was then maintained for two weeks (chronic starvation). The rats of different ages of 4 or 8 weeks were used to represent early and late adolescent animals, respectively. The complete absence of a menstrual cycle was defined as the primary outcome parameter. Acute starvation caused a disruption of the oestrous cycle in 58% of the animals. During chronic starvation, a complete loss of the oestrous cycle could be found. Furthermore, 4-week-old rats exhibited higher levels of hyperactivity and amenorrhoea than 8-week-old animals. A 20% starvation level led to 90% loss of cycle, while a 25% starvation level triggered complete loss. Most current ABA models focus on acute starvation, while most patients are chronically ill. The optimal parameters to achieve complete amenorrhoea included early adolescence, chronic starvation and 25% weight loss. The new ABA model allows studying the effects of chronic AN on underlying behavioural, hormonal and brain pathobiology. Copyright © 2017 Elsevier B.V. All rights reserved.

Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents.

PubMed

Albaugh, Vance L; Henry, Cathy R; Bello, Nicholas T; Hajnal, Andras; Lynch, Susan L; Halle, Beth; Lynch, Christopher J

2006-01-01

To characterize a model of atypical antipsychotic drug-induced obesity and evaluate its mechanism. Chronically, olanzapine or clozapine was self-administered via cookie dough to rodents (Sprague-Dawley or Wistar rats; C57Bl/6J or A/J mice). Chronic studies measured food intake, body weight, adiponectin, active ghrelin, leptin, insulin, tissue wet weights, glucose, clinical chemistry endpoints, and brain dopaminergic D2 receptor density. Acute studies examined food intake, ghrelin, leptin, and glucose tolerance. Olanzapine (1 to 8 mg/kg), but not clozapine, increased body weight in female rats only. Weight changes were detectable within 2 to 3 days and were associated with hyperphagia starting approximately 24 hours after the first dose. Chronic administration (12 to 29 days) led to adiposity, hyperleptinemia, and mild insulin resistance; no lipid abnormalities or changes in D2 receptor density were observed. Topiramate, which has reversed weight gain from atypical antipsychotics in humans, attenuated weight gain in rats. Acutely, olanzapine, but not clozapine, lowered plasma glucose and leptin. Increases in glucose, insulin, and leptin following a glucose challenge were also blunted. A model of olanzapine-induced obesity was characterized which shares characteristics of patients with atypical antipsychotic drug-induced obesity; these characteristics include hyperphagia, hyperleptinemia, insulin resistance, and weight gain attenuation by topiramate. This model may be a useful and inexpensive model of uncomplicated obesity amenable to rapid screening of weight loss drugs. Olanzapine-induced weight gain may be secondary to hyperphagia associated with acute lowering of plasma glucose and leptin, as well as the inability to increase plasma glucose and leptin following a glucose challenge.

Comparing observed and predicted mortality among ICUs using different prognostic systems: why do performance assessments differ?

PubMed

Kramer, Andrew A; Higgins, Thomas L; Zimmerman, Jack E

2015-02-01

To compare ICU performance using standardized mortality ratios generated by the Acute Physiology and Chronic Health Evaluation IVa and a National Quality Forum-endorsed methodology and examine potential reasons for model-based standardized mortality ratio differences. Retrospective analysis of day 1 hospital mortality predictions at the ICU level using Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum models on the same patient cohort. Forty-seven ICUs at 36 U.S. hospitals from January 2008 to May 2013. Eighty-nine thousand three hundred fifty-three consecutive unselected ICU admissions. None. We assessed standardized mortality ratios for each ICU using data for patients eligible for Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum predictions in order to compare unit-level model performance, differences in ICU rankings, and how case-mix adjustment might explain standardized mortality ratio differences. Hospital mortality was 11.5%. Overall standardized mortality ratio was 0.89 using Acute Physiology and Chronic Health Evaluation IVa and 1.07 using National Quality Forum, the latter having a widely dispersed and multimodal standardized mortality ratio distribution. Model exclusion criteria eliminated mortality predictions for 10.6% of patients for Acute Physiology and Chronic Health Evaluation IVa and 27.9% for National Quality Forum. The two models agreed on the significance and direction of standardized mortality ratio only 45% of the time. Four ICUs had standardized mortality ratios significantly less than 1.0 using Acute Physiology and Chronic Health Evaluation IVa, but significantly greater than 1.0 using National Quality Forum. Two ICUs had standardized mortality ratios exceeding 1.75 using National Quality Forum, but nonsignificant performance using Acute Physiology and Chronic Health Evaluation IVa. Stratification by patient and institutional characteristics indicated that units caring for more severely ill patients and those with a higher percentage of patients on mechanical ventilation had the most discordant standardized mortality ratios between the two predictive models. Acute Physiology and Chronic Health Evaluation IVa and National Quality Forum models yield different ICU performance assessments due to differences in case-mix adjustment. Given the growing role of outcomes in driving prospective payment patient referral and public reporting, performance should be assessed by models with fewer exclusions, superior accuracy, and better case-mix adjustment.

Development and validation of a prediction model for functional decline in older medical inpatients.

PubMed

Takada, Toshihiko; Fukuma, Shingo; Yamamoto, Yosuke; Tsugihashi, Yukio; Nagano, Hiroyuki; Hayashi, Michio; Miyashita, Jun; Azuma, Teruhisa; Fukuhara, Shunichi

2018-05-17

To prevent functional decline in older inpatients, identification of high-risk patients is crucial. The aim of this study was to develop and validate a prediction model to assess the risk of functional decline in older medical inpatients. In this retrospective cohort study, patients ≥65 years admitted acutely to medical wards were included. The healthcare database of 246 acute care hospitals (n = 229,913) was used for derivation, and two acute care hospitals (n = 1767 and 5443, respectively) were used for validation. Data were collected using a national administrative claims and discharge database. Functional decline was defined as a decline of the Katz score at discharge compared with on admission. About 6% of patients in the derivation cohort and 9% and 2% in each validation cohort developed functional decline. A model with 7 items, age, body mass index, living in a nursing home, ambulance use, need for assistance in walking, dementia, and bedsore, was developed. On internal validation, it demonstrated a c-statistic of 0.77 (95% confidence interval (CI) = 0.767-0.771) and good fit on the calibration plot. On external validation, the c-statistics were 0.79 (95% CI = 0.77-0.81) and 0.75 (95% CI = 0.73-0.77) for each cohort, respectively. Calibration plots showed good fit in one cohort and overestimation in the other one. A prediction model for functional decline in older medical inpatients was derived and validated. It is expected that use of the model would lead to early identification of high-risk patients and introducing early intervention. Copyright © 2018 Elsevier B.V. All rights reserved.

A mathematical model of phosphorylation AKT in Acute Myeloid Leukemia

NASA Astrophysics Data System (ADS)

Adi, Y. A.; Kusumo, F. A.; Aryati, L.; Hardianti, M. S.

2016-04-01

In this paper we consider a mathematical model of PI3K/AKT signaling pathways in phosphorylation AKT. PI3K/AKT pathway is an important mediator of cytokine signaling implicated in regulation of hematopoiesis. Constitutive activation of PI3K/AKT signaling pathway has been observed in Acute Meyloid Leukemia (AML) it caused by the mutation of Fms-like Tyrosine Kinase 3 in internal tandem duplication (FLT3-ITD), the most common molecular abnormality associated with AML. Depending upon its phosphorylation status, protein interaction, substrate availability, and localization, AKT can phosphorylate or inhibite numerous substrates in its downstream pathways that promote protein synthesis, survival, proliferation, and metabolism. Firstly, we present a mass action ordinary differential equation model describing AKT double phosphorylation (AKTpp) in a system with 11 equations. Finally, under the asumtion enzyme catalyst constant and steady state equilibrium, we reduce the system in 4 equation included Michaelis Menten constant. Simulation result suggested that a high concentration of PI3K and/or a low concentration of phospatase increased AKTpp activation. This result also indicates that PI3K is a potential target theraphy in AML.

Acute Hendra virus infection: Analysis of the pathogenesis and passive antibody protection in the hamster model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guillaume, Vanessa; Ecole Normale Superieure de Lyon, Lyon, F-69007; IFR128 BioSciences Lyon-Gerland Lyon-Sud, University of Lyon 1, 21 Avenue Tony Garnier, 69365 Lyon Cedex 07

2009-05-10

Hendra virus (HeV) and Nipah virus (NiV) are recently-emerged, closely related and highly pathogenic paramyxoviruses. We have analysed here the pathogenesis of the acute HeV infection using the new animal model, golden hamster (Mesocricetus auratus), which is highly susceptible to HeV infection. HeV-specific RNA and viral antigens were found in multiple organs and virus was isolated from different tissues. Dual pathogenic mechanism was observed: parenchymal infection in various organs, including the brain, with vasculitis and multinucleated syncytia in many blood vessels. Furthermore, monoclonal antibodies specific for the NiV fusion protein neutralized HeV in vitro and efficiently protected hamsters from HeVmore » if given before infection. These results reveal the similarities between HeV and NiV pathogenesis, particularly in affecting both respiratory and neuronal system. They demonstrate that hamster presents a convenient novel animal model to study HeV infection, opening new perspectives to evaluate vaccine and therapeutic approaches against this emergent infectious disease.« less

Renal function and acute heart failure outcome.

PubMed

Llauger, Lluís; Jacob, Javier; Miró, Òscar

2018-06-05

The interaction between acute heart failure (AHF) and renal dysfunction is complex. Several studies have evaluated the prognostic value of this syndrome. The aim of this systematic review, which includes non-selected samples, was to investigate the impact of different renal function variables on the AHF prognosis. The categories included in the studies reviewed included: creatinine, blood urea nitrogen (BUN), the BUN/creatinine quotient, chronic kidney disease, the formula to estimate the glomerular filtration rate, criteria of acute renal injury and new biomarkers of renal damage such as neutrophil gelatinase-associated lipocalin (NGAL and cystatin c). The basal alterations of the renal function, as well as the acute alterations, transient or not, are related to a worse prognosis in AHF, it is therefore necessary to always have baseline, acute and evolutive renal function parameters. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

NASA Space Radiation Risk Project: Overview and Recent Results

NASA Technical Reports Server (NTRS)

Blattnig, Steve R.; Chappell, Lori J.; George, Kerry A.; Hada, Megumi; Hu, Shaowen; Kidane, Yared H.; Kim, Myung-Hee Y.; Kovyrshina, Tatiana; Norman, Ryan B.; Nounu, Hatem N.;

Serum from CCl4-induced acute rat injury model induces differentiation of ADSCs towards hepatic cells and reduces liver fibrosis.

PubMed

Baig, Maria Tayyab; Ali, Gibran; Awan, Sana Javaid; Shehzad, Umara; Mehmood, Azra; Mohsin, Sadia; Khan, Shaheen N; Riazuddin, Sheikh

2017-10-01

Cellular therapies hold promise to alleviate liver diseases. This study explored the potential of allogenic serum isolated from rat with acute CCl 4 injury to differentiate adipose derived stem cells (ADSCs) towards hepatic lineage. Acute liver injury was induced by CCl 4 which caused significant increase in serum levels of VEGF, SDF1α and EGF. ADSCs were preconditioned with 3% serum isolated from normal and acute liver injury models. ADSCs showed enhanced expression of hepatic markers (AFP, albumin, CK8 and CK19). These differentiated ADSCs were transplanted intra-hepatically in CCl 4 -induced liver fibrosis model. After one month of transplantation, fibrosis and liver functions (alkaline phosphatase, ALAT and bilirubin) showed marked improvement in acute injury group. Elevated expression of hepatic (AFP, albumin, CK 18 and HNF4a) and pro survival markers (PCNA and VEGF) and improvement in liver architecture as deduced from results of alpha smooth muscle actin, Sirius red and Masson's trichome staining was observed.

Differentiating Acute Otitis Media and Acute Mastoiditis in Hospitalized Children.

PubMed

Laulajainen-Hongisto, Anu; Aarnisalo, Antti A; Jero, Jussi

2016-10-01

Acute otitis media is a common infection in children. Most acute otitis media episodes can be treated at an outpatient setting with antimicrobials, or only expectant observation. Hospital treatment with parenteral medication, and myringotomy or tympanostomy, may be needed to treat those with severe, prolonged symptoms, or with complications. The most common intratemporal complication of acute otitis media is acute mastoiditis. If a child with acute mastoiditis does not respond to this treatment, or if complications develop, further examinations and other surgical procedures, including mastoidectomy, are considered. Since the treatment of complicated acute otitis media and complicated acute mastoiditis differs, it is important to differentiate these two conditions. This article focuses on the differential diagnostics of acute otitis media and acute mastoiditis in children.

The influence of acute stress on the regulation of conditioned fear

PubMed Central

Raio, Candace M.; Phelps, Elizabeth A.

2014-01-01

Fear learning and regulation is a prominent model for describing the pathogenesis of anxiety disorders and stress-related psychopathology. Fear expression can be modulated using a number of regulatory strategies, including extinction, cognitive emotion regulation, avoidance strategies and reconsolidation. In this review, we examine research investigating the effects of acute stress and stress hormones on these regulatory techniques. We focus on what is known about the impact of stress on the ability to flexibly regulate fear responses that are acquired through Pavlovian fear conditioning. Our primary aim is to explore the impact of stress on fear regulation in humans. Given this, we focus on techniques where stress has been linked to alterations of fear regulation in humans (extinction and emotion regulation), and briefly discuss other techniques (avoidance and reconsolidation) where the impact of stress or stress hormones have been mainly explored in animal models. These investigations reveal that acute stress may impair the persistent inhibition of fear, presumably by altering prefrontal cortex function. Characterizing the effects of stress on fear regulation is critical for understanding the boundaries within which existing regulation strategies are viable in everyday life and can better inform treatment options for those who suffer from anxiety and stress-related psychopathology. PMID:25530986

Search for infective mammalian type-C virus-related genes in the DNA of human sarcomas and leukemias.

PubMed

Nicolson, M O; Gilden, R V; Charman, H; Rice, N; Heberling, R; McAllister, R M

1978-06-15

DNA was extracted from two human sarcoma cell lines, TE-32 and TE-418, and the leukemic cells from five children with acute myelocytic leukemia, three children with acute lymphocytic leukemia and four adults with acute myelocytic leukemia. The DNAs, assayed for infectivity by transfection techniques, induced no measurable virus by methods which would detect known mammalian C-type antigens or RNA-directed DNA polymerase in TE-32, D-17 dog cells and other indicator cells, nor did they recombine with or rescue endogenous human or exogenous murine or baboon type-C virus. Model systems used as controls were human sarcoma cells, TE-32 and HT-1080, and human lymphoma cells TE-543, experimentally infected with KiMuLV, GaLV or baboon type-C virus, all of which released infectious virus and whose DNAs were infectious for TE-32 and D-17 dog cells. Other model systems included two baboon placentas and one embryonic cell strain spontaneously releasing infectious endogenous baboon virus and yielding DNAs infectious for D-17 dog cells but not for TE-32 cells. Four other baboon embryonic tissues and two embryonic cell strains, releasing either low levels of virus or no virus, did not yield infectious DNA.

Observing the work of the Clinical Nurse Specialist: a pilot study.

PubMed

Darmody, Julie V

2005-01-01

The Clinical Nurse Specialist (CNS) is an advanced practice nurse (APN) with graduate preparation as a clinical expert within a specialty area of nursing practice. There is a need for information about the work of the CNS in order to link CNS activities to outcomes and costs of care. To describe the work of the CNS in the acute care setting using the National Association of Clinical Nurse Specialists (NACNS) model as an organizing framework. Descriptive pilot study of the work of the CNS in acute care. A 500-bed academic medical center located in the Midwestern United States. Five masters-prepared APNs in a unit-based CNS role. Direct observation and time study were used to record activities and time for 4 hours with each CNS (n = 5) for a total of 20 hours of observation. CNS activity and time within each practice domain included patient/client (30%), nursing (44%), organization/system (10%), and other activities (16%). Specific activities observed were linked to possible outcomes in the NACNS framework. The NACNS model provided a useful framework for developing a data collection tool that can be used in a larger study that analyzes the work of the acute care CNS. Describing the work of the CNS is an important preliminary step to measuring outcomes and costs of care.

Methodology for a Community Based Stroke Preparedness Intervention: The ASPIRE Study

PubMed Central

Boden-Albala, Bernadette; Edwards, Dorothy F.; Clair, Shauna St; Wing, Jeffrey J; Fernandez, Stephen; Gibbons, Chris; Hsia, Amie W.; Morgenstern, Lewis B.; Kidwell, Chelsea S.

2014-01-01

Background and Purpose Acute stroke education has focused on stroke symptom recognition. Lack of education about stroke preparedness and appropriate actions may prevent people from seeking immediate care. Few interventions have rigorously evaluated preparedness strategies in multiethnic community settings. Methods The Acute Stroke Program of Interventions Addressing Racial and Ethnic Disparities (ASPIRE) project is a multi-level program utilizing a community engaged approach to stroke preparedness targeted to underserved black communities in the District of Columbia (DC). This intervention aimed to decrease acute stroke presentation times and increase intravenous tissue plasminogen activator (IV tPA) utilization for acute ischemic stroke. Results Phase 1 included: 1) enhancement of EMS focus on acute stroke; 2) hospital collaborations to implement and/or enrich acute stroke protocols and transition DC hospitals toward Primary Stroke Center certification; and 3) pre-intervention acute stroke patient data collection in all 7 acute care DC hospitals. A community advisory committee, focus groups, and surveys identified perceptions of barriers to emergency stroke care. Phase 2 included a pilot intervention and subsequent citywide intervention rollout. A total of 531 community interventions were conducted with over 10,256 participants reached; 3289 intervention evaluations were performed, and 19,000 preparedness bracelets and 14,000 stroke warning magnets were distributed. Phase 3 included an evaluation of EMS and hospital processes for acute stroke care and a yearlong post-intervention acute stroke data collection period to assess changes in IV tPA utilization. Conclusions We report the methods, feasibility, and pre-intervention data collection efforts of the ASPIRE intervention. PMID:24876243

[Implications of nutritional status for onset and characteristics of experimental acute pancreatitis in a mouse model].

PubMed

Arndt, S; Meyer, F; Brandt-Nedelev, B; Wartmann, T; Lippert, H; Halangk, W

2013-08-01

Due to uncontrolled activation of digestive enzymes produced within the pancreas, acute pancreatitis is a disease with a great potential for complications and variable course. Since the pathophysiological steps of human pancreatitis can only be inadequately investigated, various animal models were established to study the course of disease. The model of supramaximal caerulein stimulation allows to gain insights into intracellular events of the early phase of acute pancreatitis. Usually, overnight fasted animals are used for the model of acute pancreatitis to achieve a maximum zymogen granula accumulation and a standardised initial situation due to diminished secretion of CCK. Furthermore, the role of the nutritional state for pathogenesis and course of acute pancreatitis is controversially discussed. The aim of the study was to investigate the impact of the nutritional status on pancreatic injury in experimental acute pancreatitis. Using standardised supramaximal caerulein stimulation (dose: 50 µg/kg; time intervals, 1/h; max. 7×), acute oedematous interstitial pancreatitis in fasted and non-fasted mice was induced. Pancreatic injury was locally characterised by pancreatic oedema, histopathological alterations and the release of pancreatic enzyme to the serum while systemic alterations were objectified by IL-6, CRP und pulmonal MPO. 1) Increased pancreatic serum enzyme levels after induction of acute pancreatitis in non-fasted animals do not reflect a greater affection of the pancreas since amylase and lipase in serum and pancreatic tissue correlate proportionally. The induction of acute pancreatitis provoked release of 1.3 % and 0.7 % of amylase and lipase, respectively, independently of nutritional status. 2) Neither local nor systemic parameters of pancreatic injury were significantly altered by the nutritional regimen. Pathohistologic investigations revealed increase of zymogen granula portion and cell size in non-fasted mice but no further differences compared with fasted animals. 3) During a 16-hour recovery period (no further caerulein injection), local and systemic parameters normalised. In the relatively mild model of pancreatitis induced by hormonal hyperstimulation, there was no greater pancreatic injury despite higher intrapancreatic enzyme accumulation in non-fasted animals indicating a steady state between potentially damaging and protective factors and mechanisms. Georg Thieme Verlag KG Stuttgart · New York.

Coronary heart disease is not significantly linked to acute kidney injury identified using Acute Kidney Injury Group criteria.

PubMed

Yayan, Josef

2012-01-01

Patients with unstable angina or myocardial infarction are at risk of acute kidney injury, which may be aggravated by the iodine-containing contrast agent used during coronary angiography; however, the relationship between these two conditions remains unclear. The current study investigated the relationship between acute kidney injury and coronary heart disease prior to coronary angiography. All patients were evaluated after undergoing coronary angiography in the cardiac catheterization laboratory of the Vinzentius Hospital in Landau, Germany, in 2011. The study group included patients with both acute coronary heart disease and acute kidney injury (as defined according to the classification of the Acute Kidney Injury Group); the control group included patients without acute coronary heart disease. Serum creatinine profiles were evaluated in all patients, as were a variety of demographic and health characteristics. Of the 303 patients examined, 201 (66.34%) had coronary artery disease. Of these, 38 (18.91%) also had both acute kidney injury and acute coronary heart disease prior to and after coronary angiography, and of which in turn 34 (16.91%) had both acute kidney injury and acute coronary heart disease only prior to the coronary angiography. However, the occurrence of acute kidney injury was not significantly related to the presence of coronary heart disease (P = 0.95, Chi-square test). The results of this study indicate that acute kidney injury is not linked to acute coronary heart disease. However, physicians should be aware that many coronary heart patients may develop kidney injury while hospitalized for angiography.

Evaluation of a prognostic scoring system for dogs managed with hemodialysis.

PubMed

Perondi, Francesca; Lippi, Ilaria; Ceccherini, Gianila; Marchetti, Veronica; Bernicchi, Lucrezia; Guidi, Grazia

2018-06-24

To investigate prognostic models in a cohort of dogs with acute kidney injury (AKI) and acute on chronic kidney disease (AKI/CKD) managed by hemodialysis. Retrospective study from July 2011 to November 2014. University Veterinary Teaching Hospital. Forty dogs with historical, clinical, imaging, and laboratory findings consistent with AKI or AKI/CKD managed with intermittent hemodialysis were included. Scoring system models previously established by Segev et al for outcome prediction in dogs with AKI were applied to all dogs. Models A, B, and C correctly classified outcomes in 68%, 83%, and 85% of cases, respectively. In our cohort Model A showed sensitivity of 58% and specificity of 86%, Model B showed sensitivity of 79% and specificity of 87%, Model C showed sensitivity of 86% and specificity of 84%. The presence of anuria (P < 0.0002), respiratory complications (P < 0.0001), disseminated intravascular coagulation (DIC) (P = 0.0004), grade of AKI (P = 0.0023), pancreatitis (P = 0.0001), and systemic inflammatory response syndrome (SIRS) (P = 0.0001) was significantly higher in nonsurvivors compared with survivors. In our cohort of patients, Segev's model C showed the best sensitivity and specificity for predicting prognosis, while model A had lower sensitivity. In our cohort of dialysis patients, the presence of respiratory complications, DIC, SIRS, and pancreatitis at hospitalization, were correlated with a poor prognosis. © Veterinary Emergency and Critical Care Society 2018.

Potential role of the glycolytic oscillator in acute hypoxia in tumors

NASA Astrophysics Data System (ADS)

Che Fru, Leonard; Adamson, Erin B.; Campos, David D.; Fain, Sean B.; Jacques, Steven L.; van der Kogel, Albert J.; Nickel, Kwang P.; Song, Chihwa; Kimple, Randall J.; Kissick, Michael W.

2015-12-01

Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent magnetic resonance imaging, we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.

Comparison of two models for evaluation histopathology of experimental renal ischemia.

PubMed

Tirapelli, L F; Barione, D F; Trazzi, B F M; Tirapelli, D P C; Novas, P C; Silva, C S; Martinez, M; Costa, R S; Tucci, S; Suaid, H J; Cologna, A J; Martins, A C P

2009-12-01

Renal ischemia/reperfusion (I/R) injury is one of the frequent causes of acute renal failure (ARF) due to the complex, interrelated sequence of events, that result in damage to and death of kidney cells. Cells of the proximal tubular epithelium are especially susceptible to I/R injury, leading to acute tubular necrosis, which plays a pivotal role in the pathogenesis of ARF. Several models have been explicated to assess morphological changes, including those of Jabonski et al. and Goujon et al. We compared the 2 models for histopathological evaluation of 30- or 120-minute periods of renal ischemia followed by 24-hour reperfusion in rats. Several changes were observed after application of the 2 models: proximal tubular cell necrosis, loss of brush border, vacuolization, denudation of tubular basement membrane as a consequence of flattening of basal cells, and presence of intratubular exfoliated cells in the lumen of proximal convoluted tubules at various stages of degeneration (karyorexis, kariopyknosis and karyolysis). Evaluating tubular lesions after 2 periods of experimental ischemia with light microscopy allowed us to conclude that the Goujon classification better characterized the main changes in cortical renal tubules after ischemia.

Influence of manual therapy on functional mobility after joint injury in a rat model.

PubMed

Ruhlen, Rachel L; Snider, Eric J; Sargentini, Neil J; Worthington, Bart D; Singh, Vineet K; Pazdernik, Vanessa K; Johnson, Jane C; Degenhardt, Brian F

2013-10-01

Animal models can be used to investigate manual therapy mechanisms, but testing manipulation in animal models is problematic because animals cannot directly report their pain. To develop a rat model of inflammatory joint injury to test the efficacy of manual therapy in reducing nociception and restoring function. The authors induced acute inflammatory joint injury in rats by injecting carrageenan into the ankle and then measured voluntary running wheel activity in treated and untreated rats. Treatments included manual therapy applied to the ankle and knee of the injured limb and several analgesic medications (eg, morphine, ketorolac, prednisone). Intra-articular injection of carrageenan to the ankle produced significant swelling (diameter of the ankle increased by 64% after injection; P=.004) and a robust reduction in voluntary running wheel activity (running distance reduced by 91% compared with controls; P<.001). Injured rats gradually returned to running levels equal to controls over 10 days. Neither manual therapy nor analgesic medications increased running wheel activity relative to untreated rats. Voluntary running wheel activity appears to be an appropriate functional measure to evaluate the impact of an acute inflammatory joint injury. However, efforts to treat the injury did not restore running relative to untreated rats.

CRHR1 Gene SNPs and Response to Systemic Corticosteroids in Indian Asthmatic Children During Acute Exacerbation.

PubMed

Awasthi, Shally; Gupta, Sarika; Agarwal, Sarita; Sharma, Neeraj

2015-09-01

To determine association of corticotrophin releasing hormone receptor 1 (CRHR1) gene single nucleotide polymorphisms (SNPs), rs242939 (A>G) and rs242941 (G>T) with response to systemic corticosteroids in North Indian asthmatic children during acute exacerbation. This was a hospital based cross-sectional study. Sixty-eight children aged 1 to 12 y with acute exacerbation of asthma were included in the study. The study was approved by the institutional ethics committee and written informed consent was obtained from parents/guardians of recruited children. GINA guidelines 2008, were used for classification and treatment of acute exacerbation of asthma. As per the GINA guidelines 2008, children who had good response to injectable corticosteroid were classified as "Corticosteroid Responders" (CR). Rest of the children with incomplete or poor response to injectable corticosteroid were classified as "Corticosteroid Non Responders" (CNR). Among 68 hospitalized children, 45 (66.17 %) children were CR whereas 23 (33.83 %) children were CNR. On analyzing as dominant model, children with one or two copies of mutant allele of SNP rs242941 had statistically significant better response to systemic corticosteroid (OR = 5.00; 95 %CI = 1.32-19.64; p 0.013) as compared to children with no mutant allele. Thus, CRHR1 gene SNP rs242941 polymorphism is associated with better response to systemic corticosteroid during acute exacerbation of asthma.

Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.

PubMed

Warren-Gash, Charlotte; Smeeth, Liam; Hayward, Andrew C

2009-10-01

Cardiac complications of influenza infection, such as myocarditis, are well recognised, but the role of influenza as a trigger of acute myocardial infarction is less clear. We did a systematic review of the evidence that influenza (including influenza-like illness and acute respiratory infection) triggers acute myocardial infarction or cardiovascular death. We examined the effectiveness of influenza vaccines at protecting against cardiac events and did a meta-analysis of data from randomised controlled trials. 42 publications describing 39 studies were identified. Many observational studies in different settings with a range of methods reported consistent associations between influenza and acute myocardial infarction. There was weaker evidence of an association with cardiovascular death. Two small randomised trials assessed the protection provided by influenza vaccine against cardiac events in people with existing cardiovascular disease. Whereas one trial found that influenza vaccination gave significant protection against cardiovascular death, the other trial was inconclusive. A pooled estimate from a random-effects model suggests a protective, though non-significant, effect (relative risk 0.51, 95% CI 0.15-1.76). We believe influenza vaccination should be encouraged wherever indicated, especially in people with existing cardiovascular disease, among whom there is often suboptimum vaccine uptake. Further evidence is needed on the effectiveness of influenza vaccines to reduce the risk of cardiac events in people without established vascular disease.

The role of maladaptive appraisals in child acute stress reactions.

PubMed

Salmon, Karen; Sinclair, Emma; Bryant, Richard A

2007-06-01

To test the prediction of cognitive models of trauma that negative, catastrophic appraisals central to the development of psychopathological stress reactions. A cross-sectional, concurrent design was used. Sixty-six children (aged 7-13 years), who were hospitalized after traumatic injury were assessed within 4 weeks of their trauma for acute stress disorder, depression, and administered the Child Post-traumatic Cognitions Inventory (cPTCI). Parental acute stress was also assessed. Children's negative appraisals of their ongoing vulnerability accounted for 44% of the variance of acute stress reactions in children. Injury severity, depression, age, and parental acute stress levels did not account for significant additional variance. The findings provide support for cognitive models of trauma adaptation and highlight the importance of assessing children's appraisals of their traumatic experience in order to develop effective interventions.

Common Disorders of the Pancreas

MedlinePlus

... way to confirm the diagnosis of pancreatic disease. Acute Pancreatitis Acute pancreatitis is a sudden attack causing inflammation of ... severe and last several days. Other symptoms of acute pancreatitis include nausea, vomiting, diarrhea, bloating, and fever. ...

Discriminative ability of reflex receptive fields to distinguish patients with acute and chronic low back pain.

PubMed

Müller, Monika; Biurrun Manresa, José A; Treichel, Fabienne; Agten, Christoph A; Heini, Paul; Andersen, Ole K; Curatolo, Michele; Jüni, Peter

2016-12-01

Low back pain has a life time prevalence of 70% to 85%. Approximately 10% to 20% of all patients experience recurrent episodes or develop chronic low back pain. Sociodemographic, clinical, and psychological characteristics explain the transition from acute to chronic low back pain only to a limited extent. Altered central pain processing may be a contributing mechanism. The measurement of reflex receptive fields (RRF) is a novel method to assess altered central pain processing. The RRF area denotes the area of the foot sole from which spinal nociceptive reflexes can be elicited. It was shown to be enlarged in patients with acute and chronic low back pain compared with pain-free individuals. The aim of the study was to explore the discriminative ability of the RRF to distinguish patients with acute and chronic low back pain with the hypothesis that enlarged RRF are associated with chronic low back pain. We included 214 patients with either acute or chronic low back pain and compared RRF between groups in both univariable and multivariable analyses adjusted for different sociodemographic and clinical characteristics possibly associated with the transition to chronic pain. We found a mean difference between patients with acute and chronic low back pain of -0.01 (95% confidence interval [CI], -0.06 to 0.04) in the crude, -0.02 (95% CI, -0.08 to 0.04) in the age and sex adjusted, and -0.02 (95% CI, -0.09 to 0.05) in the fully adjusted model. Our results suggest that the enlargement of RRF area may not be associated with the transition from acute to chronic low back pain.

Value of the Delta Neutrophil Index for Predicting 28-Day Mortality in Patients With Acute Pulmonary Embolism in the Emergency Department.

PubMed

Kong, Taeyoung; Park, Yoo Seok; Lee, Hye Sun; Kim, Sinae; Lee, Jong Wook; Yu, Gina; Eun, Claire; You, Je Sung; Chung, Hyun Soo; Park, Incheol; Chung, Sung Phil

2018-06-01

Acute pulmonary embolism (PE), frequently seen in the emergency department (ED), is a leading cause of cardiovascular morbidity and mortality. The delta neutrophil index (DNI) reflects the fraction of circulating immature granulocytes as a component of the systemic inflammatory response syndrome criteria. The pathogenesis of acute PE is significantly associated with inflammation. The aim of the study was to investigate the clinical usefulness of the DNI as a marker of severity in patients with acute PE admitted to the ED. We retrospectively analyzed the data of patients who were diagnosed with acute PE at a single ED, admitted from January 1, 2011 to June 30, 2017. The diagnosis of acute pulmonary embolism was confirmed using clinical, laboratory, and radiological findings. The DNI was determined at presentation. The clinical outcome was all-cause mortality within 28 days of emergency department admission. We included 447 patients in this study. The multivariate Cox regression model demonstrated that higher DNI values on ED admission were significantly associated with short-term mortality (hazard ratio, 1.107; 95% confidence interval, 1.042-1.177). The optimal cut-off DNI value, measured on ED admission, was 3.0%; this value was associated with an increased hazard of 28-day mortality following PE (HR, 7.447; 95% CI, 4.183-13.366; P < 0.001) CONCLUSION:: The DNI value, obtained as part of the complete blood count analysis, can be easily determined without additional burdens of cost or time. A high DNI is useful as a marker to predict 28-day mortality in patients with acute PE.

Experimental evidence of obesity as a risk factor for severe acute pancreatitis.

PubMed

Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

2009-11-14

The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimize the therapy and to prevent organ dysfunction and local complications. For that purpose, multiple clinical scale scores have been applied to patients with acute pancreatitis. Recently, a new problem has emerged: the increased severity of the disease in obese patients. However, the mechanisms by which obesity increases the severity of acute pancreatitis are unclear. Several hypotheses have been suggested: (1) obese patients have an increased inflammation within the pancreas; (2) obese patients have an increased accumulation of fat within and around the pancreas where necrosis is often located; (3) increase in both peri- and intra-pancreatic fat and inflammatory cells explain the high incidence of pancreatic inflammation and necrosis in obese patients; (4) hepatic dysfunction associated with obesity might enhance the systemic inflammatory response by altering the detoxification of inflammatory mediators; and (5) ventilation/perfusion mismatch leading to hypoxia associated with a low pancreatic flow might reduce the pancreatic oxygenation and further enhance pancreatic injury. Recent experimental investigations also show an increased mortality and morbidity in obese rodents with acute pancreatitis and the implication of the adipokines leptin and adiponectin. Such models are important to investigate whether the inflammatory response of the disease is enhanced by obesity. It is exciting to speculate that manipulation of the adipokine milieu has the potential to influence the severity of acute pancreatitis.

Acute opioid withdrawal is associated with increased neural activity in reward-processing centers in healthy men: A functional magnetic resonance imaging study.

PubMed

Chu, Larry F; Lin, Joanne C; Clemenson, Anna; Encisco, Ellen; Sun, John; Hoang, Dan; Alva, Heather; Erlendson, Matthew; Clark, J David; Younger, Jarred W

2015-08-01

Opioid analgesics are frequently prescribed for chronic pain. One expected consequence of long-term opioid use is the development of physical dependence. Although previous resting state functional magnetic resonance imaging (fMRI) studies have demonstrated signal changes in reward-associated areas following morphine administration, the effects of acute withdrawal on the human brain have been less well-investigated. In an earlier study by our laboratory, ondansetron was shown to be effective in preventing symptoms associated with opioid withdrawal. The purpose of this current study was to characterize neural activity associated with acute opioid withdrawal and examine whether these changes are modified by ondansetron. Ten participants were enrolled in this placebo-controlled, randomized, double-blind, crossover study and attended three acute opioid withdrawal sessions. Participants received either placebo or ondansetron (8Ymg IV) before morphine administration (10Ymg/70Ykg IV). Participants then underwent acute naloxone-precipitated withdrawal during a resting state fMRI scan. Objective and subjective opioid withdrawal symptoms were assessed. Imaging results showed that naloxone-precipitated opioid withdrawal was associated with increased neural activity in several reward processing regions, including the right pregenual cingulate, putamen, and bilateral caudate, and decreased neural activity in networks involved in sensorimotor integration. Ondansetron pretreatment did not have a significant effect on the imaging correlates of opioid withdrawal. This study presents a preliminary investigation of the regional changes in neural activity during acute opioid withdrawal. The fMRI acute opioid withdrawal model may serve as a tool for studying opioid dependence and withdrawal in human participants. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Rationale and design of a randomized trial of home electronic symptom and lung function monitoring to detect cystic fibrosis pulmonary exacerbations: the early intervention in cystic fibrosis exacerbation (eICE) trial.

PubMed

Lechtzin, N; West, N; Allgood, S; Wilhelm, E; Khan, U; Mayer-Hamblett, N; Aitken, M L; Ramsey, B W; Boyle, M P; Mogayzel, P J; Goss, C H

2013-11-01

Acute pulmonary exacerbations are central events in the lives of individuals with cystic fibrosis (CF). Pulmonary exacerbations lead to impaired lung function, worse quality of life, and shorter survival. We hypothesized that aggressive early treatment of acute pulmonary exacerbation may improve clinical outcomes. Describe the rationale of an ongoing trial designed to determine the efficacy of home monitoring of both lung function measurements and symptoms for early detection and subsequent early treatment of acute CF pulmonary exacerbations. A randomized, non-blinded, multi-center trial in 320 individuals with CF aged 14 years and older. The study compares usual care to a twice a week assessment of home spirometry and CF respiratory symptoms using an electronic device with data transmission to the research personnel to identify and trigger early treatment of CF pulmonary exacerbation. Participants will be enrolled in the study for 12 months. The primary endpoint is change in FEV1 (L) from baseline to 12 months determined by a linear mixed effects model incorporating all quarterly FEV1 measurements. Secondary endpoints include time to first acute protocol-defined pulmonary exacerbation, number of acute pulmonary exacerbations, number of hospitalization days for acute pulmonary exacerbation, time from the end of acute pulmonary exacerbation to onset of subsequent pulmonary exacerbation, change in health related quality of life, change in treatment burden, change in CF respiratory symptoms, and adherence to the study protocol. This study is a first step in establishing alternative approaches to the care of CF pulmonary exacerbations. We hypothesize that early treatment of pulmonary exacerbations has the potential to slow lung function decline, reduce respiratory symptoms and improve the quality of life for individuals with CF. © 2013.

Estimation of reliability of predictions and model applicability domain evaluation in the analysis of acute toxicity (LD50).

PubMed

Sazonovas, A; Japertas, P; Didziapetris, R

2010-01-01

This study presents a new type of acute toxicity (LD(50)) prediction that enables automated assessment of the reliability of predictions (which is synonymous with the assessment of the Model Applicability Domain as defined by the Organization for Economic Cooperation and Development). Analysis involved nearly 75,000 compounds from six animal systems (acute rat toxicity after oral and intraperitoneal administration; acute mouse toxicity after oral, intraperitoneal, intravenous, and subcutaneous administration). Fragmental Partial Least Squares (PLS) with 100 bootstraps yielded baseline predictions that were automatically corrected for non-linear effects in local chemical spaces--a combination called Global, Adjusted Locally According to Similarity (GALAS) modelling methodology. Each prediction obtained in this manner is provided with a reliability index value that depends on both compound's similarity to the training set (that accounts for similar trends in LD(50) variations within multiple bootstraps) and consistency of experimental results with regard to the baseline model in the local chemical environment. The actual performance of the Reliability Index (RI) was proven by its good (and uniform) correlations with Root Mean Square Error (RMSE) in all validation sets, thus providing quantitative assessment of the Model Applicability Domain. The obtained models can be used for compound screening in the early stages of drug development and prioritization for experimental in vitro testing or later in vivo animal acute toxicity studies.

[Establishment of comprehensive prediction model of acute gastrointestinal injury classification of critically ill patients].

PubMed

Wang, Yan; Wang, Jianrong; Liu, Weiwei; Zhang, Guangliang

2018-03-25

To develop the comprehensive prediction model of acute gastrointestinal injury (AGI) grades of critically ill patients. From April 2015 to November 2015, the binary channel gastrointestinal sounds (GIS) monitor system which has been developed and verified by the research group was used to gather and analyze the GIS of 60 consecutive critically ill patients who were admitted in Critical Care Medicine of Chinese PLA General Hospital. Also, the AGI grades (Grande I(-IIII(, the higher the level, the heavier the gastrointestinal dysfunction) were evaluated. Meanwhile, the clinical data and physiological and biochemical indexes of included patients were collected and recorded daily, including illness severity score (APACHE II( score, consisting of the acute physiology score, age grade and chronic health evaluation), sequential organ failure assessment (SOFA score, including respiration, coagulation, liver, cardioascular, central nervous system and kidney) and Glasgow coma scale (GCS); body mass index, blood lactate and glucose, and treatment details (including mechanical ventilation, sedatives, vasoactive drugs, enteral nutrition, etc.) Then principal component analysis was performed on the significantly correlated GIS (five indexes of gastrointestinal sounds were found to be negatively correlated with AGI grades, which included the number, percentage of time, mean power, maximum power and maximum time of GIS wave from the channel located at the stomach) and clinical factors after standardization. The top 5 post-normalized main components were selected for back-propagation (BP) neural network training, to establish comprehensive AGI grades models of critically ill patients based on the neural network model. The 60 patients aged 19 to 98 (mean 54.6) years and included 42 males (70.0%). There were 22 cases of multiple fractures, 15 cases of severe infection, 7 cases of cervical vertebral fracture, 7 cases of aortic repair, 5 cases of post-toxicosis and 4 cases of cerebral trauma. There were 33 emergency operation, 10 cases of elecoperectomy and 17 cases of drug treatment. There were 56 cases of diabetes(93.3%). Forty-five cases (75.0%) used vasoactive drugs, 37 cases (61.7%) used mechanical ventilation and 44 cases (73.3%) used enteral nutrition. APACHE II( score were 4.0 to 28.0(average 16.8) points. Four clinical factors were significantly positively related with AGI grades, including lactic acid level (r=0.215, P=0.000), SOFA score (r=0.383, P=0.000), the use of vascular active drugs (r=0.611, P=0.000) and mechanical ventilation (r=0.142, P=0.014). In addition to the five indexes of gastric bowel sounds which were found to be negatively correlated with AGI grades, the characteristics of 333 by 9 were composed of these nine indexes with high correlation of AGI grades. Five main components were selected after principal component analysis of these nine correlated indexes. A comprehensive AGI grades model of critically ill patients with a fitting degree of 0.967 3 and an accuracy rate of 82.61% was built by BP artificial neural network. The comprehensive model to classify AGI grades with the GIS is developed, which can help further predicting the classification of AGI grades of critically ill patients.

Comparison of radial 4D Flow-MRI with perivascular ultrasound to quantify blood flow in the abdomen and introduction of a porcine model of pre-hepatic portal hypertension.

PubMed

Frydrychowicz, A; Roldan-Alzate, A; Winslow, E; Consigny, D; Campo, C A; Motosugi, U; Johnson, K M; Wieben, O; Reeder, S B

2017-12-01

Objectives of this study were to compare radial time-resolved phase contrast magnetic resonance imaging (4D Flow-MRI) with perivascular ultrasound (pvUS) and to explore a porcine model of acute pre-hepatic portal hypertension (PHTN). Abdominal 4D Flow-MRI and pvUS in portal and splenic vein, hepatic and both renal arteries were performed in 13 pigs of approximately 60 kg. In six pigs, measurements were repeated after partial portal vein (PV) ligature. Inter- and intra-reader comparisons and statistical analysis including Bland-Altman (BA) comparison, paired Student's t tests and linear regression were performed. PvUS and 4D Flow-MRI measurements agreed well; flow before partial PV ligature was 322 ± 30 ml/min in pvUS and 297 ± 27 ml/min in MRI (p = 0.294), and average BA difference was 25 ml/min [-322; 372]. Inter- and intra-reader results differed very little, revealed excellent correlation (R 2  = 0.98 and 0.99, respectively) and resulted in BA differences of -5 ml/min [-161; 150] and -2 ml/min [-28; 25], respectively. After PV ligature, PV flow decreased from 356 ± 50 to 298 ± 61 ml/min (p = 0.02), and hepatic arterial flow increased from 277 ± 36 to 331 ± 65 ml/min (p = n.s.). The successful in vivo comparison of radial 4D Flow-MRI to perivascular ultrasound revealed good agreement of abdominal blood flow although with considerable spread of results. A model of pre-hepatic PHTN was successfully introduced and acute responses monitored. • Radial 4D Flow-MRI in the abdomen was successfully compared to perivascular ultrasound. • Inter- and intra-reader testing demonstrated excellent reproducibility of upper abdominal 4D Flow-MRI. • A porcine model of acute pre-hepatic portal hypertension was successfully introduced. • 4D Flow-MRI successfully monitored acute changes in a model of portal hypertension.

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair.

PubMed

Ford, James B; Baturin, Dmitry; Burleson, Tamara M; Van Linden, Annemie A; Kim, Yong-Mi; Porter, Christopher C

2015-09-29

While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine and that mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia.

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair

PubMed Central

Burleson, Tamara M.; Van Linden, Annemie A.; Kim, Yong-Mi; Porter, Christopher C.

2015-01-01

While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine. Mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia. PMID:26334102

Volume of Plasma Expansion and Functional Outcomes in Stroke.

PubMed

Miller, Joseph B; Lewandowski, Christopher; Wira, Charles R; Taylor, Andrew; Burmeister, Charlotte; Welch, Robert

2017-04-01

Plasma expansion in acute ischemic stroke has potential to improve cerebral perfusion, but the long-term effects on functional outcome are mixed in prior trials. The goal of this study was to evaluate how the magnitude of plasma expansion affects neurological recovery in acute stroke. This was a secondary analysis of data from the Albumin in Acute Stroke Part 2 trial investigating the relationship between the magnitude of overall intravenous volume infusion (crystalloid and colloid) to clinical outcome. The data were inclusive of 841 patients with a mean age of 64 years and a median National Institutes of Health Stroke Scale (NIHSS) of 11. In a multivariable-adjusted logistic regression model, this analysis tested the volume of plasma expansion over the first 48 h of hospitalization as a predictor of favorable outcome, defined as either a modified Rankin Scale score of 0 or 1 or a NIHSS score of 0 or 1 at 90 days. This model included all study patients, irrespective of albumin or isotonic saline treatment. Patients that received higher volumes of plasma expansion more frequently had large vessel ischemic stroke and higher NIHSS scores. The multivariable-adjusted model revealed that there was decreased odds of a favorable outcome for every 250 ml additional volume plasma expansion over the first 48 h (OR 0.91, 95 % CI, 0.88-0.94). The present study demonstrates an association between greater volume of plasma expansion and worse neurological recovery.

Increased oxidative phosphorylation in response to acute and chronic DNA damage

PubMed Central

Brace, Lear E; Vose, Sarah C; Stanya, Kristopher; Gathungu, Rose M; Marur, Vasant R; Longchamp, Alban; Treviño-Villarreal, Humberto; Mejia, Pedro; Vargas, Dorathy; Inouye, Karen; Bronson, Roderick T; Lee, Chih-Hao; Neilan, Edward; Kristal, Bruce S; Mitchell, James R

2016-01-01

Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa−/−|Xpa−/− mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo. In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes. PMID:28721274

The Balanced Scorecard of acute settings: development process, definition of 20 strategic objectives and implementation.

PubMed

Groene, Oliver; Brandt, Elimer; Schmidt, Werner; Moeller, Johannes

2009-08-01

Strategy development and implementation in acute care settings is often restricted by competing challenges, the pace of policy reform and the existence of parallel hierarchies. To describe a generic approach to strategy development, illustrate the use of the Balanced Scorecard as a tool to facilitate strategy implementation and demonstrate how to break down strategic goals into measurable elements. Multi-method approach using three different conceptual models: Health Promoting Hospitals Standards and Strategies, the European Foundation for Quality Management (EFQM) Model and the Balanced Scorecard. A bundle of qualitative and quantitative methods were used including in-depth interviews, standardized organization-wide surveys on organizational values, staff satisfaction and patient experience. Three acute care hospitals in four different locations belonging to a German holding group. Chief executive officer, senior medical officers, working group leaders and hospital staff. Development and implementation of the Balanced Scorecard. Twenty strategic objectives with corresponding Balanced Scorecard measures. A stepped approach from strategy development to implementation is presented to identify key themes for strategy development, drafting a strategy map and developing strategic objectives and measures. The Balanced Scorecard, in combination with the EFQM model, is a useful tool to guide strategy development and implementation in health care organizations. As for other quality improvement and management tools not specifically developed for health care organizations, some adaptations are required to improve acceptability among professionals. The step-wise approach of strategy development and implementation presented here may support similar processes in comparable organizations.

Targeting aspirin in acute disabling ischemic stroke: an individual patient data meta-analysis of three large randomized trials.

PubMed

Thompson, Douglas D; Murray, Gordon D; Candelise, Livia; Chen, Zhengming; Sandercock, Peter A G; Whiteley, William N

2015-10-01

Aspirin is of moderate overall benefit for patients with acute disabling ischemic stroke. It is unclear whether functional outcome could be improved after stroke by targeting aspirin to patients with a high risk of recurrent thrombosis or a low risk of haemorrhage. We aimed to determine whether patients at higher risk of thrombotic events or poor functional outcome, or lower risk of major haemorrhage had a greater absolute risk reduction of poor functional outcome with aspirin than the average patient. We used data on individual ischemic stroke patients from three large trials of aspirin vs. placebo in acute ischemic stroke: the first International Stroke Trial (n = 18,372), the Chinese Acute Stroke Trial (n = 20,172) and the Multicentre Acute Stroke Trial (n = 622). We developed and evaluated clinical prediction models for the following: early thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis and pulmonary embolism); early haemorrhagic events (significant intracranial haemorrhage, major extracranial haemorrhage, or haemorrhagic transformation of an infarct); and late poor functional outcome. We calculated the absolute risk reduction of poor functional outcome (death or dependence) at final follow-up in: quartiles of early thrombotic risk; quartiles of early haemorrhagic risk; and deciles of poor functional outcome risk. Ischemic stroke patients who were older, had lower blood pressure, computerized tomography evidence of infarct or more severe deficits due to stroke had increased risk of thrombotic and haemorrhagic events and poor functional outcome. Prediction models built with all baseline variables (including onset to treatment time) discriminated weakly between patients with and without recurrent thrombotic events (area under the receiver operating characteristic curve 0·56, 95% CI:0·53-0·59) and haemorrhagic events (0·57, 0·52-0·64), though well between patients with and without poor functional outcome (0·77, 0·76-0·78) in the International Stroke Trial. We found no evidence that the net benefit of aspirin increased with increasing risk of thrombosis, haemorrhage or poor functional outcome in all three trials. Using simple clinical variables to target aspirin to patients after acute disabling stroke by risk of thrombosis, haemorrhage or poor functional outcome does not lead to greater net clinical benefit. We suggest future risk stratification schemes include new risk factors for thrombosis and intracranial haemorrhage. © 2015 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Prevalence of Imaging Biomarkers to Guide the Planning of Acute Stroke Reperfusion Trials.

PubMed

Jiang, Bin; Ball, Robyn L; Michel, Patrik; Jovin, Tudor; Desai, Manisha; Eskandari, Ashraf; Naqvi, Zack; Wintermark, Max

2017-06-01

Imaging biomarkers are increasingly used as selection criteria for stroke clinical trials. The goal of our study was to determine the prevalence of commonly studied imaging biomarkers in different time windows after acute ischemic stroke onset to better facilitate the design of stroke clinical trials using such biomarkers for patient selection. This retrospective study included 612 patients admitted with a clinical suspicion of acute ischemic stroke with symptom onset no more than 24 hours before completing baseline imaging. Patients with subacute/chronic/remote infarcts and hemorrhage were excluded from this study. Imaging biomarkers were extracted from baseline imaging, which included a noncontrast head computed tomography (CT), perfusion CT, and CT angiography. The prevalence of dichotomized versions of each of the imaging biomarkers in several time windows (time since symptom onset) was assessed and statistically modeled to assess time dependence (not lack thereof). We created tables showing the prevalence of the imaging biomarkers pertaining to the core, the penumbra and the arterial occlusion for different time windows. All continuous imaging features vary over time. The dichotomized imaging features that vary significantly over time include: noncontrast head computed tomography Alberta Stroke Program Early CT (ASPECT) score and dense artery sign, perfusion CT infarct volume, and CT angiography collateral score and visible clot. The dichotomized imaging features that did not vary significantly over time include the thresholded perfusion CT penumbra volumes. As part of the feasibility analysis in stroke clinical trials, this analysis and the resulting tables can help investigators determine sample size and the number needed to screen. © 2017 American Heart Association, Inc.

Utilization of ICU Data to Improve 30 and 60 Day HENRE Mortality Models, Revision 1

DTIC Science & Technology

2017-05-12

Acute Radiation Syndrome , Mortality, Burn Combined Injury, Lethality, Small Intestine, Ordinary...a large dose of radiation in a short period of time (high dose rate) causes acute radiation syndrome (ARS). Depending on the radiation dose, an...individual may experience the hematopoietic acute radiation syndrome (H-ARS) or the gastrointestinal acute radiation syndrome (GI-ARS) (reviewed in

Team Performance and Risk-Adjusted Health Outcomes in the Program of All-Inclusive Care for the Elderly (PACE)

ERIC Educational Resources Information Center

Mukamel, Dana B.; Temkin-Greener, Helena; Delavan, Rachel; Peterson, Derick R.; Gross, Diane; Kunitz, Stephen; Williams, T. Franklin

2006-01-01

Purpose: The Program of All-Inclusive Care for the Elderly (PACE) is a community-based program providing primary, acute, and long-term care to frail elderly individuals. A central component of the PACE model is the interdisciplinary care team, which includes both professionals and non-professionals. The purpose of this study was to examine the…

Phosphorescence In Bacillus Spores

DTIC Science & Technology

2003-07-01

commonly causing acute otitis media (middle ear infections) is present in an animal model. We will briefly review this application since it shows that...causing acute otitis media in a chinchilla model. Laryngoscope.110, 1119-1123, (2000). 2. C.D. Bluestone, J.O. Klein, Otitis media , atelesctasis

Does adherence to treatment mediate the relationship between patients' treatment outcome expectancies and the outcomes of pain intensity and recovery from acute low back pain?

PubMed

Haanstra, Tsjitske M; Kamper, Steven J; Williams, Christopher M; Spriensma, Alette S; Lin, Chung-Wei Christine; Maher, Christopher G; de Vet, Henrica C W; Ostelo, Raymond W J G

2015-08-01

It is believed that patients' expectancies about the effectiveness of treatment influence their treatment outcomes, but the working mechanism is rarely studied in patients with low back pain. Theoretical models suggest that adherence to treatment may be an important pathway. The aim of this study was to assess the mediating role of adherence to treatment in the relationship between expectancies and the outcomes of recovery and pain intensity in patients with acute low back pain. This study used data from a randomized placebo-controlled trial of paracetamol for acute low back pain. Expectancies were measured with the Credibility Expectancy Questionnaire. Adherence was measured with a medication diary. Pain intensity was recorded daily in a diary on a 0 to 10 pain scale, and recovery was defined as the first of 7 consecutive days scoring 0 or 1 on a 6-point pain scale. Cox regression (dependent variable: recovery) and linear mixed-model analyses (dependent variable: daily pain intensity scores) were performed. The "difference in coefficients" approach was used to establish mediation. A total of 1573 participants were included in current analyses. There was a small but highly significant relationship between expectancies and outcomes; 3.3% of the relationship between expectancies and recovery and 14.2% of the relationship between expectancies and pain intensity were mediated by adherence to treatment. This study does not convincingly support the theory that adherence is a key pathway in the relationship between treatment outcome expectancies and recovery and pain intensity in this acute low back pain population.

Evaluation of the NICE mini-GRACE risk scores for acute myocardial infarction using the Myocardial Ischaemia National Audit Project (MINAP) 2003-2009: National Institute for Cardiovascular Outcomes Research (NICOR).

PubMed

Simms, Alexander D; Reynolds, Stephanie; Pieper, Karen; Baxter, Paul D; Cattle, Brian A; Batin, Phillip D; Wilson, John I; Deanfield, John E; West, Robert M; Fox, Keith A A; Hall, Alistair S; Gale, Christopher P

2013-01-01

To evaluate the performance of the National Institute for Health and Clinical Excellence (NICE) mini-Global Registry of Acute Coronary Events (GRACE) (MG) and adjusted mini-GRACE (AMG) risk scores. Retrospective observational study. 215 acute hospitals in England and Wales. 137 084 patients discharged from hospital with a diagnosis of acute myocardial infarction (AMI) between 2003 and 2009, as recorded in the Myocardial Ischaemia National Audit Project (MINAP). Model performance indices of calibration accuracy, discriminative and explanatory performance, including net reclassification index (NRI) and integrated discrimination improvement. Of 495 263 index patients hospitalised with AMI, there were 53 196 ST elevation myocardial infarction and 83 888 non-ST elevation myocardial infarction (NSTEMI) (27.7%) cases with complete data for all AMG variables. For AMI, AMG calibration was better than MG calibration (Hosmer-Lemeshow goodness of fit test: p=0.33 vs p<0.05). MG and AMG predictive accuracy and discriminative ability were good (Brier score: 0.10 vs 0.09; C statistic: 0.82 and 0.84, respectively). The NRI of AMG over MG was 8.1% (p<0.05). Model performance was reduced in patients with NSTEMI, chronic heart failure, chronic renal failure and in patients aged ≥85 years. The AMG and MG risk scores, utilised by NICE, demonstrated good performance across a range of indices using MINAP data, but performed less well in higher risk subgroups. Although indices were better for AMG, its application may be constrained by missing predictors.

Comprehensive mollusk acute toxicity database improves the use of Interspecies Correlation Estimation (ICE) models to predict toxicity of untested freshwater and endangered mussel species

EPA Science Inventory

Interspecies correlation estimation (ICE) models extrapolate acute toxicity data from surrogate test species to untested taxa. A suite of ICE models developed from a comprehensive database is available on the US Environmental Protection Agency’s web-based application, Web-I...

Derivation and external validation of a case mix model for the standardized reporting of 30-day stroke mortality rates.

PubMed

Bray, Benjamin D; Campbell, James; Cloud, Geoffrey C; Hoffman, Alex; James, Martin; Tyrrell, Pippa J; Wolfe, Charles D A; Rudd, Anthony G

2014-11-01

Case mix adjustment is required to allow valid comparison of outcomes across care providers. However, there is a lack of externally validated models suitable for use in unselected stroke admissions. We therefore aimed to develop and externally validate prediction models to enable comparison of 30-day post-stroke mortality outcomes using routine clinical data. Models were derived (n=9000 patients) and internally validated (n=18 169 patients) using data from the Sentinel Stroke National Audit Program, the national register of acute stroke in England and Wales. External validation (n=1470 patients) was performed in the South London Stroke Register, a population-based longitudinal study. Models were fitted using general estimating equations. Discrimination and calibration were assessed using receiver operating characteristic curve analysis and correlation plots. Two final models were derived. Model A included age (<60, 60-69, 70-79, 80-89, and ≥90 years), National Institutes of Health Stroke Severity Score (NIHSS) on admission, presence of atrial fibrillation on admission, and stroke type (ischemic versus primary intracerebral hemorrhage). Model B was similar but included only the consciousness component of the NIHSS in place of the full NIHSS. Both models showed excellent discrimination and calibration in internal and external validation. The c-statistics in external validation were 0.87 (95% confidence interval, 0.84-0.89) and 0.86 (95% confidence interval, 0.83-0.89) for models A and B, respectively. We have derived and externally validated 2 models to predict mortality in unselected patients with acute stroke using commonly collected clinical variables. In settings where the ability to record the full NIHSS on admission is limited, the level of consciousness component of the NIHSS provides a good approximation of the full NIHSS for mortality prediction. © 2014 American Heart Association, Inc.

Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

NASA Astrophysics Data System (ADS)

Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

2014-03-01

Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

Age-Related Effects of Alcohol from Adolescent, Adult, and Aged Populations Using Human and Animal Models

PubMed Central

Squeglia, Lindsay M.; Boissoneault, Jeff; Van Skike, Candice E.; Nixon, Sara Jo; Matthews, Douglas B.

2014-01-01

Background This review incorporates current research examining alcohol's differential effects on adolescents, adults, and aged populations in both animal and clinical models. Methods The studies presented range from cognitive, behavioral, molecular, and neuroimaging techniques, leading to a more comprehensive understanding of how acute and chronic alcohol use affects the brain throughout the life span. Results Age of life is a significant factor in determining the effect of alcohol on brain functioning. Adolescents and aged populations may be more negatively affected by heavy alcohol use when compared to adults. Conclusions Investigations limiting alcohol effects to a single age group constrains understanding of differential trajectories and outcomes following acute and chronic use. To meaningfully address the sequencing and interaction effects of alcohol and age, the field must incorporate collaborative and integrated research efforts focused on interdisciplinary questions facilitated by engaging basic and applied scientists with expertise in a range of disciplines including alcohol, neurodevelopment, and aging. PMID:25156779

Insulin signaling is acutely required for long-term memory in Drosophila.

PubMed

Chambers, Daniel B; Androschuk, Alaura; Rosenfelt, Cory; Langer, Steven; Harding, Mark; Bolduc, Francois V

2015-01-01

Memory formation has been shown recently to be dependent on energy status in Drosophila. A well-established energy sensor is the insulin signaling (InS) pathway. Previous studies in various animal models including human have revealed the role of insulin levels in short-term memory but its role in long-term memory remains less clear. We therefore investigated genetically the spatial and temporal role of InS using the olfactory learning and long-term memory model in Drosophila. We found that InS is involved in both learning and memory. InS in the mushroom body is required for learning and long-term memory whereas long-term memory specifically is impaired after InS signaling disruption in the ellipsoid body, where it regulates the level of p70s6k, a downstream target of InS and a marker of protein synthesis. Finally, we show also that InS is acutely required for long-term memory formation in adult flies.

Next Generation Respiratory Viral Vaccine System: Advanced and Emerging Bioengineered Human Lung Epithelia Model (HLEM) Organoid Technology

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; Schneider, Sandra L.; MacIntosh, Victor; Gibbons, Thomas F.

2010-01-01

Acute respiratory infections, including pneumonia and influenza, are the S t" leading cause of United States and worldwide deaths. Newly emerging pathogens signaled the need for an advanced generation of vaccine technology.. Human bronchial-tracheal epithelial tissue was bioengineered to detect, identify, host and study the pathogenesis of acute respiratory viral disease. The 3-dimensional (3D) human lung epithelio-mesechymal tissue-like assemblies (HLEM TLAs) share characteristics with human respiratory epithelium: tight junctions, desmosomes, microvilli, functional markers villin, keratins and production of tissue mucin. Respiratory Syntial Virus (RSV) studies demonstrate viral growth kinetics and membrane bound glycoproteins up to day 20 post infection in the human lung-orgainoid infected cell system. Peak replication of RSV occurred on day 10 at 7 log10 particles forming units per ml/day. HLEM is an advanced virus vaccine model and biosentinel system for emergent viral infectious diseases to support DoD global surveillance and military readiness.

Anti-inflammatory and antinociceptive activities of azadirachtin in mice.

PubMed

Soares, Darly G; Godin, Adriana M; Menezes, Raquel R; Nogueira, Rafaela D; Brito, Ana Mercy S; Melo, Ivo S F; Coura, Giovanna Maria E; Souza, Danielle G; Amaral, Flávio A; Paulino, Tony P; Coelho, Márcio M; Machado, Renes R

2014-06-01

Azadirachta indica (Meliaceae) extracts have been reported to exhibit anti-inflammatory and antinociceptive properties. However, the activities of azadirachtin, a limonoid and the major bioactive compound found in the extracts, have been poorly investigated in animal models. In the present study, we investigated the effects induced by azadirachtin in experimental models of pain and inflammation in mice. Carrageenan-induced paw edema and fibrovascular tissue growth induced by subcutaneous cotton pellet implantation were used to investigate the anti-inflammatory activity of azadirachtin in mice. Zymosan-induced writhing and hot plate tests were employed to evaluate the antinociceptive activity. To explore putative mechanisms of action, the level of tumor necrosis factor-α in inflammatory tissue was measured and the effect induced by opioidergic and serotonergic antagonists was evaluated. Previous per os (p. o.) administration of azadirachtin (120 mg/kg) significantly reduced the acute paw edema induced by carrageenan. However, the concomitant increase of the paw concentration of tumor necrosis factor-α induced by this inflammatory stimulus was not reduced by azadirachtin. In addition to inhibiting the acute paw edema induced by carrageenan, azadirachtin (6, 60, and 120 mg/kg) inhibited the proliferative phase of the inflammatory response, as demonstrated by the reduced formation of fibrovascular tissue growth. Azadirachtin (120 mg/kg) also inhibited the nociceptive response in models of nociceptive (hot plate) and inflammatory (writhing induced by zymosan) pain. The activity of azadirachtin (120 mg/kg) in the model of nociceptive pain was attenuated by a nonselective opioid antagonist, naltrexone (10 mg/kg, i. p.), but not by a nonselective serotonergic antagonist, cyproheptadine. In conclusion, this study demonstrates the activity of azadirachtin in experimental models of nociceptive and inflammatory pain, and also in models of acute and chronic inflammation. Finally, multiple mechanisms, including the inhibition of the production of inflammatory mediators and activation of endogenous opioid pathways, may mediate azadirachtin activities in experimental models of inflammation and pain. Georg Thieme Verlag KG Stuttgart · New York.

Care Offered by an Information-Rich Pediatric Acute Illness Connected Care Model.

PubMed

McConnochie, Kenneth M; Wood, Nancy E; Alarie, Carol; Ronis, Sarah

2016-06-01

Prevailing regulatory and financing issues constrain dissemination of connected care despite evidence supporting acceptability, effectiveness, and efficiency. In this analysis we describe care provided over a 12-year period by Health-e-Access, an evidence-based, information-rich, connected care model designed to serve children with acute illness. We demonstrate the broad clinical capacity of this care model and key components imparting this capacity. Since 2001, Health-e-Access has been used in childcare, elementary schools, neighborhood after-hours sites, and a school for children with severe disabilities in Rochester, NY. With Health-e-Access, videoconference (preferably) or telephone enables parent, patient, and provider engagement. Technology includes the capacity for acquisition and exchange of a broad range of clinical observations, qualifying Health-e-Access as an information-rich model and differentiating it from multiple other connected care models commonly labeled telemedicine. Primary diagnoses recorded for completed visits were classified according to resources (technology, personnel, examination type) required to complete encounters appropriately. Among 13,812 Health-e-Access visits initiated through June 2013, 98.2% were completed. Capacity for ear-nose-throat examination and close inspection of eye and skin were sufficient to identify positive findings supporting 95.2% of primary diagnoses. Videoconference and stethoscope were considered essential for observations required to rule out serious conditions often presenting in similar fashion to these 95%. Health-e-Access included technology essential for establishing diagnoses, ruling out more serious conditions, and identifying problems beyond its scope. Regulations enabling and financing incentivizing replication of similar connected care models would benefit families and communities substantially. Observations challenge regulatory bodies and payers to support connected health services of comparable value.

The older persons' assessment and liaison team 'OPAL': evaluation of comprehensive geriatric assessment in acute medical inpatients.

PubMed

Harari, D; Martin, F C; Buttery, A; O'Neill, S; Hopper, A

2007-11-01

Reducing hospital length of stay (LOS) in older acute medical inpatients is a key productivity measure. Evidence-based predictors of greater LOS may be targeted through Comprehensive Geriatric Assessment (CGA). Evaluate a novel service model for CGA screening of older acute medical inpatients linked to geriatric intervention. Urban teaching hospital. Acute medical inpatients aged 70+ years. Multidisciplinary CGA screening of all acute medical admissions aged 70+ years leading to (a) rapid transfer to geriatric wards or (b) case-management on general medical wards by Older Persons Assessment and Liaison team (OPAL). Prospective pre-post comparison with statistical adjustment for baseline factors, and use of national benchmarking LOS data. Pre-OPAL (n = 46) and post-OPAL (n = 49) cohorts were similarly identified as high-risk by the CGA screening tool, but only post-OPAL patients received the intervention. Pre-OPAL, 0% fallers versus 92% post-OPAL were specifically assessed and/or referred to a falls service post-discharge. Management of delirium, chronic pain, constipation, and urinary incontinence similarly improved. Over twice as many patients were transferred to geriatric wards, with mean days from admission to transfer falling from 10 to 3. Mean LOS fell by 4 days post-OPAL. Only the OPAL intervention was associated with LOS (P = 0.023) in multiple linear regression including case-mix variables (e.g. age, function, 'geriatric giants'). Benchmarking data showed the LOS reduction to be greater than comparable hospitals. CGA screening of acute medical inpatients leading to early geriatric intervention (ward-based case management, appropriate transfer to geriatric wards), improved clinical effectiveness and general hospital performance.

The effects of acute inflammation on cognitive functioning and emotional processing in humans: A systematic review of experimental studies.

PubMed

Bollen, Jessica; Trick, Leanne; Llewellyn, David; Dickens, Chris

2017-03-01

The cognitive neuropsychological model of depression proposes that negative biases in the processing of emotionally salient information have a central role in the development and maintenance of depression. We have conducted a systematic review to determine whether acute experimental inflammation is associated with changes to cognitive and emotional processing that are thought to cause and maintain depression. We identified experimental studies in which healthy individuals were administered an acute inflammatory challenge (bacterial endotoxin/vaccination) and standardised tests of cognitive function were performed. Fourteen references were identified, reporting findings from 12 independent studies on 345 participants. Methodological quality was rated strong or moderate for 11 studies. Acute experimental inflammation was triggered using a variety of agents (including endotoxin from E. coli, S. typhi, S. abortus Equi and Hepatitis B vaccine) and cognition was assessed over hours to months, using cognitive tests of i) attention/executive functioning, ii) memory and iii) social/emotional processing. Studies found mixed evidence that acute experimental inflammation caused changes to attention/executive functioning (2 of 6 studies showed improvements in attention executive function compared to control), changes in memory (3 of 5 studies; improved reaction time: reduced memory for object proximity: poorer immediate and delayed memory) and changes to social/emotional processing (4 of 5 studies; reduced perception of emotions, increased avoidance of punishment/loss experiences, and increased social disconnectedness). Acute experimental inflammation causes negative biases in social and emotional processing that could explain observed associations between inflammation and depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute and chronic disability among U.S. farmers and pesticide applicators: the National Health Interview Survey (NHIS).

PubMed

Gómez-Marín, O; Fleming, L E; Lee, D J; LeBlanc, W; Zheng, D; Ma, F; Jané, D; Pitman, T; Caban, A

2004-11-01

The National Health Interview Survey (NHIS) is a multipurpose household survey of the U.S. civilian non-institutionalized population conducted annually since 1957. From 1986 to 1994, over 450,000 U.S. workers, age 18 years and older, participated in a probability sampling of the entire non-institutionalized U.S. population; variables collected included a range of measures of acute and chronic disability. The objective of the present study was to assess predictors of health status, and acute and chronic disability for farmers and pesticide applicators (pesticide-exposed workers) compared to all other U.S. workers using the 1986-1994 NHIS. After adjustment for sample weights and design effects using SUDAAN, several measures of acute and chronic disability and health status were modeled with multiple logistic regression. Farmers (n = 9576) were significantly older compared to all other U.S. workers (n = 453,219) and pesticide applicators (n = 180). Farmers and pesticide applicators had a higher proportion of males, whites, and Hispanics and were less educated. After adjusting for age, gender, race-ethnicity, and education, compared to all other workers, farmers were significantly less likely to report acute and chronic disability and health conditions, while pesticide applicators were more likely to report chronic disability, health conditions, and poor health. Given the cross-sectional nature of the data and the significant job demands of farming, both leading to a relative healthy worker effect, the present results indicate that at any point in time, farmers report less acute and chronic disability, compared to other U.S. workers, whereas pesticide applicators report similar or poorer health.

Result Summary for the Area 5 Radioactive Waste Management Site Performance Assessment Model Version 4.110

DOE Office of Scientific and Technical Information (OSTI.GOV)

NSTec Environmental Management

2011-07-20

Results for Version 4.110 of the Area 5 Radioactive Waste Management Site (RWMS) performance assessment (PA) model are summarized. Version 4.110 includes the fiscal year (FY) 2010 inventory estimate, including a future inventory estimate. Version 4.110 was implemented in GoldSim 10.11(SP4). The following changes have been implemented since the last baseline model, Version 4.105: (1) Updated the inventory and disposal unit configurations with data through the end of FY 2010. (1) Implemented Federal Guidance Report 13 Supplemental CD dose conversion factors (U.S. Environmental Protection Agency, 1999). Version 4.110 PA results comply with air pathway and all-pathways annual total effective dosemore » (TED) performance objectives (Tables 2 and 3, Figures 1 and 2). Air pathways results decrease moderately for all scenarios. The time of the maximum for the air pathway open rangeland scenario shifts from 1,000 to 100 years (y). All-pathways annual TED increases for all scenarios except the resident scenario. The maximum member of public all-pathways dose occurs at 1,000 y for the resident farmer scenario. The resident farmer dose was predominantly due to technetium-99 (Tc-99) (82 percent) and lead-210 (Pb-210) (13 percent). Pb-210 present at 1,000 y is produced predominantly by radioactive decay of uranium-234 (U-234) present at the time of disposal. All results for the postdrilling and intruder-agriculture scenarios comply with the performance objectives (Tables 4 and 5, Figures 3 and 4). The postdrilling intruder results are similar to Version 4.105 results. The intruder-agriculture results are similar to Version 4.105, except for the Pit 6 Radium Disposal Unit (RaDU). The intruder-agriculture result for the Shallow Land Burial (SLB) disposal units is a significant fraction of the performance objective and exceeds the performance objective at the 95th percentile. The intruder-agriculture dose is due predominantly to Tc-99 (75 percent) and U-238 (9.5 percent). The acute intruder scenario results comply with all performance objectives (Tables 6 and 7, Figures 5 and 6). The acute construction result for the SLB disposal units decreases significantly with this version. The maximum acute intruder dose occurs at 1,000 y for the SLB disposal units under the acute construction scenario. The acute intruder dose is caused by multiple radionuclides including U-238 (31 percent), Th-229 (28 percent), plutonium-239 (8.6 percent), U-233 (7.8 percent), and U-234 (6.7 percent). All results for radon-222 (Rn-222) flux density comply with the performance objective (Table 8, Figure 7). The mean Pit 13 RaDU flux density is close to the 0.74 Bq m{sup -2} s{sup -1} limit.« less

Stress among nurses working in emergency, anesthesiology and intensive care units depends on qualification: a Job Demand-Control survey.

PubMed

Trousselard, Marion; Dutheil, Frédéric; Naughton, Geraldine; Cosserant, Sylvie; Amadon, Sylvie; Dualé, Christian; Schoeffler, Pierre

2016-02-01

The nurse stress literature reports an overwhelming culture of acceptance and expectation of work stressors, ironically linked to the control of the workplace to effectively and proactively manage stress. The stressors involved in delivering "stress management" have been well studied in nursing-related workplaces, especially in acute care settings in accordance with the Karasek Job Demand-Control-Support (JDCS) model. However, little is known about the effects of specificity of an acute care unit and the level of qualifications on stress experienced by nurses. A survey using the JDCS model was conducted among 385 nurses working in three different acute care units (anesthesiology, emergency and intensive care unit) from a university hospital. Specific questions explored variables such as gender, acute care units, level of qualification and working experience. Two hundred questionnaires were returned. A high level of job strain was highlighted without a gender effect and in the absence of isostrain. Nurses from acute care units were located in the high stress quadrant of the JDCS model. Conversely, other nurses were commonly located in the "active" quadrant. Independent of acute care settings, the highest level of education was associated with the highest job strain and the lowest level of control. In an acute care setting, a high level of education was a key factor for high job stress and was associated with a perception of a low control in the workplace, both of which may be predictors of adverse mental health. In particular, the lack of control has been associated with moral distress, a frequently reported characteristic of acute care settings. To enhance the personal and professional outcomes of the advanced registered nurses, strategies for supporting nurses manage daily stressors in acute care are urgently required.

Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

PubMed

Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

2017-02-01

Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease. Trials are needed to test existing and novel therapies in subjects with early/mild COPD to potentially reduce the risk of progressing to more advanced lung disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).

Risk factors for and the prevention of acute kidney injury after abdominal surgery.

PubMed

An, Yongbo; Shen, Kai; Ye, Yingjiang

2018-06-01

Postoperative acute kidney injury in patients undergoing abdominal surgery is not rare and often results in bad outcomes for patients. The incidence of postoperative acute kidney injury is hard to evaluate reliably due to its non-unified definitions in different studies. Risk factors for acute kidney injury specific to abdominal surgery include preoperative renal insufficiency, intraabdominal hypertension, blood transfusion, bowel preparation, perioperative dehydration, contrast agent and nephrotoxic drug use. Among these, preoperative renal insufficiency is the strongest predictor of acute kidney injury. The peri-operative management of high-risk patients should include meticulous selection of fluid solutions. Balanced crystalloid solutions and albumin are generally thought to be relatively safe, while the safety of hydroxyethyl starch solutions has been controversial. The purpose of the present review is to discuss the current knowledge regarding postoperative acute kidney injury in abdominal surgical settings to help surgeons make better decisions concerning the peri-operative management.

Electrocardiogram Changes with Acute Alcohol Intoxication: A Systematic Review.

PubMed

Raheja, Hitesh; Namana, Vinod; Chopra, Kirti; Sinha, Ankur; Gupta, Sushilkumar Satish; Kamholz, Stephan; Moskovits, Norbert; Shani, Jacob; Hollander, Gerald

2018-01-01

Acute alcohol intoxication has been associated with cardiac arrhythmias but the electrocardiogram (ECG) changes associated with acute alcohol intoxication are not well defined in the literature. Highlight the best evidence regarding the ECG changes associated with acute alcohol intoxication in otherwise healthy patients and the pathophysiology of the changes. A literature search was carried out; 4 studies relating to ECG changes with acute alcohol intoxication were included in this review. Of the total 141 patients included in the review, 90 (63.8%) patients had P-wave prolongation, 80 (56%) patients had QTc prolongation, 19 (13.5%) patients developed T-wave abnormalities, 10 (7%) patients had QRS complex prolongation, 3 (2.12%) patients developed ST-segment depressions. The most common ECG changes associated with acute alcohol intoxication are (in decreasing order of frequency) P-wave and QTc prolongation, followed by T-wave abnormalities and QRS complex prolongation. Mostly, these changes are completely reversible.

Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.

PubMed

Lindow, Janet C; Wunder, Elsio A; Popper, Stephen J; Min, Jin-Na; Mannam, Praveen; Srivastava, Anup; Yao, Yi; Hacker, Kathryn P; Raddassi, Khadir; Lee, Patty J; Montgomery, Ruth R; Shaw, Albert C; Hagan, Jose E; Araújo, Guilherme C; Nery, Nivison; Relman, David A; Kim, Charles C; Reis, Mitermayer G; Ko, Albert I

2016-11-01

Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.

Relationship of pharmaceutical promotion to antidepressant switching and adherence: a retrospective cohort study.

PubMed

Hansen, Richard A; Chen, Shih-Yin; Gaynes, Bradley N; Maciejewski, Matthew L

2010-12-01

Patient nonadherence and early discontinuation of antidepressant treatment are common. Pharmaceutical promotion to consumers and physicians may influence this behavior. The objectives of this study were to explore whether promotional spending is related to early antidepressant switching, acute-phase adherence, and continuation-phase adherence. A retrospective cohort study was conducted with national promotional expenditure data merged with medical and prescription claims data from a large national health plan affiliated with i3 Innovus. Included were records for continuously insured adults with major depression who received a new prescription for an antidepressant: 5,010 were in the cohort assessed for switching, 4,457 were in the cohort assessed for acute-phase adherence, and 1,772 were in the cohort assessed for continuation-phase adherence. National promotional efforts were estimated by examining inflation-adjusted spending on direct-to-consumer advertising (DTCA) and physician detailing. Clinical guidelines were used to create proxies for aspects of treatment outcomes, including antidepressant switching and adherence in the acute phase and adherence in the continuation phase. Logistic regression models estimated the association between promotional variables and these outcomes. Patients taking medications that were more highly promoted to physicians were less likely to switch medications (odds ratio [OR]=.61) and were more likely to be adherent during the acute phase of treatment (OR=1.13). DTCA had little effect on switching or antidepressant adherence. Detailing to physicians was associated with lower rates of medication switching and had a positive relationship with patient adherence during early antidepressant treatment. This finding indicates that certain aspects of promotion may have beneficial effects on antidepressant use.

Frequency, risk factors, and outcomes of vancomycin-resistant Enterococcus colonization and infection in patients with newly diagnosed acute leukemia: different patterns in patients with acute myelogenous and acute lymphoblastic leukemia.

PubMed

Ford, Clyde D; Lopansri, Bert K; Haydoura, Souha; Snow, Greg; Dascomb, Kristin K; Asch, Julie; Bo Petersen, Finn; Burke, John P

2015-01-01

OBJECTIVE To determine the frequency, risk factors, and outcomes for vancomycin-resistant Enterococcus (VRE) colonization and infection in patients with newly diagnosed acute leukemia. DESIGN Retrospective clinical study with VRE molecular strain typing. SETTING A regional referral center for acute leukemia. PATIENTS Two hundred fourteen consecutive patients with newly diagnosed acute leukemia between 2006 and 2012. METHODS All patients had a culture of first stool and weekly surveillance for VRE. Clinical data were abstracted from the Intermountain Healthcare electronic data warehouse. VRE molecular typing was performed utilizing the semi-automated DiversiLab System. RESULTS The rate of VRE colonization was directly proportional to length of stay and was higher in patients with acute lymphoblastic leukemia. Risk factors associated with colonization include administration of corticosteroids (P=0.004) and carbapenems (P=0.009). Neither a colonized prior room occupant nor an increased unit colonization pressure affected colonization risk. Colonized patients with acute myelogenous leukemia had an increased risk of VRE bloodstream infection (BSI, P=0.002). Other risk factors for VRE BSI include severe neutropenia (P=0.04) and diarrhea (P=0.008). Fifty-eight percent of BSI isolates were identical or related by molecular typing. Eighty-nine percent of bloodstream isolates were identical or related to stool isolates identified by surveillance cultures. VRE BSI was associated with increased costs (P=0.0003) and possibly mortality. CONCLUSIONS VRE colonization has important consequences for patients with acute myelogenous leukemia undergoing induction therapy. For febrile neutropenic patients with acute myelogenous leukemia, use of empirical antibiotic regimens that avoid carbapenems and include VRE coverage may be helpful in decreasing the risks associated with VRE BSI.

Antinociceptive Grayanoids from the Roots of Rhododendron molle.

PubMed

Li, Yong; Liu, Yun-Bao; Zhang, Jian-Jun; Liu, Yang; Ma, Shuang-Gang; Qu, Jing; Lv, Hai-Ning; Yu, Shi-Shan

2015-12-24

Nine new grayanoids (1-9), together with 11 known compounds, were isolated from the roots of Rhododendron molle. The structures of the new compounds (1-9) were determined on the basis of spectroscopic analysis, including HRESIMS, and 1D and 2D NMR data. Compounds 4, 6, 12, and 14-20 showed significant antinociceptive activities in an acetic acid-induced writhing test. In particular, 14 and 15 were found to be more potent than morphine for both acute and inflammatory pain models and 100-fold more potent than gabapentin in a diabetic neuropathic pain model.

Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells in acute liver injured mice.

PubMed

Peng, Yuan; Chen, Qian; Yang, Tao; Tao, Yanyan; Lu, Xiong; Liu, Chenghai

2014-03-01

Cultured mycelium Cordyceps sinensis (CMCS) was widely used for a variety of diseases including liver injury, the current study aims to investigate the protective effects of CMCS on liver sinusoidal endothelial cells (LSECs) in acute injury liver and related action mechanisms. The mice were injected intraperitoneally with lipopolysaccharide (LPS) and D-galactosamine (D-GalN). 39 male BABL/c mice were randomly divided into four groups: normal control, model control, CMCS treatment and 1,10-phenanthroline treatment groups. The Serum liver function parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were assayed with the commercial kit. The inflammation and scaffold structure in liver were stained with hematoxylin and eosin and silver staining respectively. The LSECs and sub-endothelial basement membrane were observed with the scanning and transmission electronic microscope. The protein expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in liver were analyzed with Western blotting. Expression of von Willebrand factor (vWF) was investigated with immunofluorescence staining. The lipid peroxidation indicators including antisuperoxideanion (ASAFR), hydroxyl free radical (·OH), superoxide dismutase (SOD), malondialdehyde and glutathione S-transferase (GST) were determined with kits, and matrix metalloproteinase-2 and 9 (MMP-2/9) activities in liver were analyzed with gelatin zymography and in situ fluorescent zymography respectively. The model mice had much higher serum levels of ALT and AST than the normal mice. Compared to that in the normal control, more severe liver inflammation and hepatocyte apoptosis, worse hepatic lipid peroxidation demonstrated by the increased ASAFR, ·OH and MDA, but decreased SOD and GST, increased MMP-2/9 activities and VCAM-1, ICAM-1 and vWF expressions, which revealed obvious LSEC injury and scaffold structure broken, were shown in the model control. Compared with the model group, CMCS and 1,10-phenanthroline significantly improved serum ALT/AST, attenuated hepatic inflammation and improved peroxidative injury in liver, decreased MMP-2/9 activities in liver tissue, improved integration of scaffold structure, and decreased protein expression of VCAM-1 and ICAM-1. CMCS could protect LSECs from injury and maintain the microvasculature integration in acute injured liver of mice induced by LPS/D-GalN. Its action mechanism was associated with the down-regulation of MMP-2/9 activities and inhibition of peroxidation in injured liver.

Models of Hemodynamics and Hematopoiesis Following Hemorrhage for Use in Combined Injury Simulations

DTIC Science & Technology

2016-06-01

Inflammation 9(1):1; 2012. Hempelmann LH, Lisco H, Hoffman JG. The acute radiation syndrome : a study of nine cases and a review of the problem. Annals of...job of capturing the acute increase of circulating granulocytes following a radiation insult compared to the model in Wentz et al. 2014 which does...19; 1995. Andrews GA, Sitterson BW, Kretchmar AL, Brucer M. Criticality accident at the Y-12 plant. Diagnosis and Treatment of Acute Radiation

ESTIMATION OF AQUATIC SPECIES SENSITIVITY USING INTERSPECIES CORRELATION AND ACUTE TO CHRONIC TOXICITY MODELS

EPA Science Inventory

Abstract for presentation

Estimation of aquatic species sensitivity using interspecies correlation and acute to chronic toxicity models

Determining species sensitivity of aquatic organisms to contaminants is a critical component of criteria development and ecolog...

Evolution of Acute Kidney Injury and Its Association With Systemic Hemodynamics in Children With Fluid-Refractory Septic Shock.

PubMed

Deep, Akash; Sagar, Hiremath; Goonasekera, Chulananda; Karthikeyan, Palaniswamy; Brierley, Joe; Douiri, Abdel

2018-07-01

There are no studies in pediatrics evaluating the progression of acute kidney injury in septic shock. We investigated the evolution of sepsis-associated acute kidney injury and its association with systemic hemodynamics in children with fluid-refractory septic shock. Prospective cohort study. PICU of a tertiary care hospital. All patients with fluid-refractory septic shock (n = 61) between September 2010 and February 2014. Hemodynamic variables using noninvasive ultrasound cardiac output monitor were measured at admission and 6 hourly thereafter till 48 hours. We used the Kidney Disease: Improving Global Outcomes criteria to define and stage acute kidney injury. Associations between various hemodynamic variables and development of acute kidney injury were evaluated. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury and was compared with no acute kidney injury or stage 1 acute kidney injury. Severe acute kidney injury developed in 29.5% (n = 18) of the 61 children with fluid-refractory septic shock, whereas 43 patients (70.49%) had either no or stage 1 acute kidney injury. Most patients who developed acute kidney injury did so within the first 48 hours of PICU admission. Severe acute kidney injury conferred a three-fold increased risk of death by day 28 (hazard ratio, 3.23; 95% CI, 1.52-6.67; p = 0.002), longer ICU stay, and increased duration of mechanical ventilation. Central venous pressure at presentation was higher in severe acute kidney injury by 5 cm H2O. Highest lactate in the first 24 hours of PICU admission, low diastolic blood pressure, low systemic vascular resistance index at admission were associated with severe acute kidney injury. This model reliably predicted stage 2/3 acute kidney injury by day 3 with area under the curve equals to 94%; 95% CI, 88.3-99.99. None of the other hemodynamic variables showed any association with severe acute kidney injury. Manifestations of sepsis-associated acute kidney injury often occur early after PICU admission and is associated with increased morbidity and mortality. There is a need to develop a predictive model in septic shock which could facilitate early detection of acute kidney injury.

Necroptosis may be a novel mechanism for cardiomyocyte death in acute myocarditis.

PubMed

Zhou, Fei; Jiang, Xuejun; Teng, Lin; Yang, Jun; Ding, Jiawang; He, Chao

2018-05-01

In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3. These findings provide evidence that necroptosis plays a significant role in cardiomyocyte death and it is a major pathway for cell death in acute VMC. Blocking the necroptosis pathway may serve as a new therapeutic option for the treatment of acute viral myocarditis.

Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases?

PubMed

Abreu, Soraia C; Weiss, Daniel J; Rocco, Patricia R M

2016-04-14

Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, proteins/peptides, mRNA, microRNA, and lipids) and/or organelles with reparative and anti-inflammatory properties to recipient cells. The paracrine anti-inflammatory effects promoted by MSC-derived EVs have attracted significant interest in the regenerative medicine field, including for potential use in lung injuries. In the present review, we describe the characteristics, biological activities, and mechanisms of action of MSC-derived EVs. We also review the therapeutic potential of EVs as reported in relevant preclinical models of acute and chronic respiratory diseases, such as pneumonia, acute respiratory distress syndrome, asthma, and pulmonary arterial hypertension. Finally, we discuss possible approaches for potentiating the therapeutic effects of MSC-derived EVs so as to enable use of this therapy in clinical practice.

Structures, processes and outcomes of the Aussie Heart Guide Program: A nurse mentor supported, home based cardiac rehabilitation program for rural patients with acute coronary syndrome.

PubMed

Frohmader, Terence J; Lin, Frances; Chaboyer, Wendy P

2018-03-01

Cardiac rehabilitation has a number of benefits for patients, yet participation in it is sub-optimal, especially in regional Australia. Innovative models of cardiac rehabilitation are needed to improve participation. Providing nurse mentors to support patients transitioning from hospital to home represents a new model of service delivery in Australia. To explore the impact of a home-based cardiac rehabilitation program in assisting patients to recover from Acute Coronary Syndrome and meeting the expectations of nurse mentors delivering the program. This case study was underpinned by the structure, process and outcomes model and occurred in three Australian hospitals 2008-2011. Thirteen patients recovering from acute coronary syndrome were interviewed by telephone and seven nurse mentors completed a survey after completing the program. Mentor perceptions concerning the structures of the home-based CR program included the timely recruitment of patients, mentor training to operationalise the program, commitment to development of the mentor role, and the acquisition of knowledge and skills about cognitive behavioural therapy and patient centred care. Processes included the therapeutic relationship between mentors and patients, suitability of the program and the promotion of healthier lifestyle behaviours. Outcomes identified that patients were satisfied with the program's audiovisual resources, and the level of support and guidance provided by their nurse mentors. Mentors believed that the program was easy to use in terms of its delivery. Patients believed the program assisted their recovery and were satisfied with the information, guidance and support received from mentors. There were positive signs that the program influenced patients' decisions to change unhealthy lifestyle behaviours. Outcomes highlighted both rewards and barriers associated with mentoring patients in their homes by telephone. Experience gained from developing a therapeutic relationship with patients during their recovery, assisted nurses in developing the mentor role. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Electrophysiological Perspectives on the Therapeutic Use of Nicotinic Acetylcholine Receptor Partial AgonistsS⃞

PubMed Central

Trocmé-Thibierge, Caryn; Guendisch, Daniela; Al Rubaiy, Shehd Abdullah Abbas; Bloom, Stephen A.

2011-01-01

Partial agonist therapies rely variously on two hypotheses: the partial agonists have their effects through chronic low-level receptor activation or the partial agonists work by decreasing the effects of endogenous or exogenous full agonists. The relative significance of these activities probably depends on whether acute or chronic effects are considered. We studied nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus laevis oocytes to test a model for the acute interactions between acetylcholine (ACh) and weak partial agonists. Data were best-fit to a basic competition model that included an additional factor for noncompetitive inhibition. Partial agonist effects were compared with the nAChR antagonist bupropion in prolonged bath application experiments that were designed to mimic prolonged drug exposure typical of therapeutic drug delivery. A primary effect of prolonged application of nicotine was to decrease the response of all nAChR subtypes to acute applications of ACh. In addition, nicotine, cytisine, and varenicline produced detectable steady-state activation of α4β2* [(α4)2(β2)3, (α4)3(β2)2, and (α4)2(β2)2α5)] receptor subtypes that was not seen with other test compounds. Partial agonists produced no detectable steady-state activation of α7 nAChR, but seemed to show small potentiation of ACh-evoked responses; however, “run-up” of α7 ACh responses was also sometimes observed under control conditions. Potential off-target effects of the partial agonists therefore included the modulation of α7 responses by α4β2 partial agonists and decreases in α4β2* responses by α7-selective agonists. These data indicate the dual effects expected for α4β2* partial agonists and provide models and insights for utility of partial agonists in therapeutic development. PMID:21285282

Acute ileitis facilitates infection with multidrug resistant Pseudomonas aeruginosa in human microbiota-associated mice.

PubMed

von Klitzing, Eliane; Ekmekciu, Ira; Bereswill, Stefan; Heimesaat, Markus M

2017-01-01

The rising incidence of multidrug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa has become a serious issue in prevention of its spread particularly among hospitalized patients. It is, however, unclear whether distinct conditions such as acute intestinal inflammation facilitate P. aeruginosa infection of vertebrate hosts. To address this, we analysed P. aeruginosa infection in human microbiota-associated (hma) mice with acute ileitis induced by peroral Toxoplasma gondii challenge. When perorally infected with P. aeruginosa at day 3 post ileitis induction, hma mice displayed higher intestinal P. aeruginosa loads as compared to hma mice without ileitis. However, the overall intestinal microbiota composition was not disturbed by P. aeruginosa (except for lowered bifidobacterial populations), and the infection did not further enhance ileal immune cell responses. Pro-inflammatory cytokines including IFN-γ and IL-12p70 were similarly increased in ileum and mesenteric lymph nodes of P. aeruginosa infected and uninfected hma mice with ileitis. The anti-inflammatory cytokine IL-10 increased multifold upon ileitis induction, but interestingly more distinctly in P. aeruginosa infected as compared to uninfected controls. Immune responses were not restricted to the intestines as indicated by elevated pro-inflammatory cytokine levels in liver and kidney upon ileitis induction. However, except for hepatic TNF-α levels, P. aeruginosa infection did not result in more distinct pro-inflammatory cytokine secretion in liver and kidney of hma mice with ileitis. Whereas viable intestinal bacteria were more frequently detected in systemic compartments such as spleen and cardiac blood of P. aeruginosa infected than uninfected mice at day 7 following ileitis induction, P. aeruginosa infection did not exacerbate systemic pro-inflammatory sequelae, but resulted in lower IL-10 serum levels. Acute intestinal inflammation facilitates infection of the vertebrate host with MDR bacteria including P. aeruginosa and might also pose particularly hospitalized patients at risk for acquisition. Since acute T. gondii induced inflammation might mask immunopathology caused by P. aeruginosa , a subacute or chronic inflammation model might be better suited to investigate the potential role of P. aeruginosa infection in the aggravation of intestinal disease.

An innovative enterostomal therapy nurse model of community wound care delivery: a retrospective cost-effectiveness analysis.

PubMed

Harris, Connie; Shannon, Ronald

2008-01-01

A Canadian specialty nursing association identified the necessity to examine the role and impact of enterostomal (ET) nursing in Canada. We completed a retrospective analysis of the cost-effectiveness and benefits of ET nurse-driven resources for the treatment of acute and chronic wounds in the community. This was a multicenter retrospective pragmatic chart audit of 3 models of nursing care utilizing 4 community nursing agencies and 1 specialty company owned and operated by ET nurses. An analysis was completed using quantitative methods to evaluate healing outcomes, nursing costs, and cost-effectiveness. Kaplan-Meier estimates were calculated to determine the average time to 100% healing of acute and chronic wounds and total nursing visit costs for treatment in a community setting. Average direct nursing costs related to management of each wound were determined by number of nursing visits and related reimbursement for each visit. A Monte Carlo simulation method was used to help account for costs and benefits in determination of cost-effectiveness between caring groups and the uncertainty from variation between patients and wounds. Three hundred sixty chronic wounds and 54 acute surgical wound charts were audited. Involvement of a registered nurse (RN) with ET or advanced wound ostomy skills (AWOS) in community-level chronic and acute wound care was associated with lower overall costs mainly due to reduced time to 100% closure of the wound and reduced number of nursing visits. The differences in health benefits and total costs of nursing care between the ET/AWOS and a hybrid group that includes interventions developed by an ET nurse and followed by general visiting nurses that could include both RNs and registered practical nurses is an expected reduction in healing times of 45 days and an expected cost difference of $5927.00 per chronic wound treated. When outcomes were broken into ET/AWOS involvement categories for treatment of chronic wounds, there was a significantly faster time to 100% closure at a lower mean cost as the ET/AWOS involvement increased in the case. For acute wound treatment, the differences in health benefits and total costs between the ET/AWOS and a hybrid nursing care model were an expected reduction in healing times of 95 days and an expected cost difference of $9578.00 per acute wound treated. Again, there was a significant difference in healing times and reduced mean cost as the ET/AWOS became more involved in the treatment. The financial benefit to the Ontario Ministry of Health and Long-Term Care is estimated to increase as the involvement of nurses with ET/AWOS specialty training increases. The greater the involvement both directly and indirectly of an ET/AWOS nurse in the management of wounds, the greater the savings and the shorter the healing times.

Consultant Input in Acute Medical Admissions and Patient Outcomes in Hospitals in England: A Multivariate Analysis

PubMed Central

Bell, Derek; Lambourne, Adrian; Percival, Frances; Laverty, Anthony A.; Ward, David K.

2013-01-01

Recent recommendations for physicians in the UK outline key aspects of care that should improve patient outcomes and experience in acute hospital care. Included in these recommendations are Consultant patterns of work to improve timeliness of clinical review and improve continuity of care. This study used a contemporaneous validated survey compared with clinical outcomes derived from Hospital Episode Statistics, between April 2009 and March 2010 from 91 acute hospital sites in England to evaluate systems of consultant cover for acute medical admissions. Clinical outcomes studied included adjusted case fatality rates (aCFR), including the ratio of weekend to weekday mortality, length of stay and readmission rates. Hospitals that had an admitting Consultant presence within the Acute Medicine Unit (AMU, or equivalent) for a minimum of 4 hours per day (65% of study group) had a lower aCFR compared with hospitals that had Consultant presence for less than 4 hours per day (p<0.01) and also had a lower 28 day re-admission rate (p<0.01). An ‘all inclusive’ pattern of Consultant working, incorporating all the guideline recommendations and which included the minimum Consultant presence of 4 hours per day (29%) was associated with reduced excess weekend mortality (p<0.05). Hospitals with >40 acute medical admissions per day had a lower aCFR compared to hospitals with fewer than 40 admissions per day (p<0.03) and had a lower 7 day re-admission rate (p<0.02). This study is the first large study to explore the potential relationships between systems of providing acute medical care and clinical outcomes. The results show an association between well-designed systems of Consultant working practices, which promote increased patient contact, and improved patient outcomes in the acute hospital setting. PMID:23613858

Consultant input in acute medical admissions and patient outcomes in hospitals in England: a multivariate analysis.

PubMed

Bell, Derek; Lambourne, Adrian; Percival, Frances; Laverty, Anthony A; Ward, David K

2013-01-01

Recent recommendations for physicians in the UK outline key aspects of care that should improve patient outcomes and experience in acute hospital care. Included in these recommendations are Consultant patterns of work to improve timeliness of clinical review and improve continuity of care. This study used a contemporaneous validated survey compared with clinical outcomes derived from Hospital Episode Statistics, between April 2009 and March 2010 from 91 acute hospital sites in England to evaluate systems of consultant cover for acute medical admissions. Clinical outcomes studied included adjusted case fatality rates (aCFR), including the ratio of weekend to weekday mortality, length of stay and readmission rates. Hospitals that had an admitting Consultant presence within the Acute Medicine Unit (AMU, or equivalent) for a minimum of 4 hours per day (65% of study group) had a lower aCFR compared with hospitals that had Consultant presence for less than 4 hours per day (p<0.01) and also had a lower 28 day re-admission rate (p<0.01). An 'all inclusive' pattern of Consultant working, incorporating all the guideline recommendations and which included the minimum Consultant presence of 4 hours per day (29%) was associated with reduced excess weekend mortality (p<0.05). Hospitals with >40 acute medical admissions per day had a lower aCFR compared to hospitals with fewer than 40 admissions per day (p<0.03) and had a lower 7 day re-admission rate (p<0.02). This study is the first large study to explore the potential relationships between systems of providing acute medical care and clinical outcomes. The results show an association between well-designed systems of Consultant working practices, which promote increased patient contact, and improved patient outcomes in the acute hospital setting.

Perceived stress at work is associated with attenuated DHEA-S response during acute psychosocial stress.

PubMed

Lennartsson, Anna-Karin; Theorell, Töres; Kushnir, Mark M; Bergquist, Jonas; Jonsdottir, Ingibjörg H

2013-09-01

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to play a protective role during acute psychosocial stress, because they act as antagonists to the effects of the stress hormone cortisol. This study aims to investigate whether prolonged psychosocial stress, measured as perceived stress at work during the past week, is related to the capacity to produce DHEA and DHEA-S during acute psychosocial stress. It also aims to investigate whether prolonged perceived stress affects the balance between production of cortisol and DHEA-S during acute psychosocial stress. Thirty-six healthy subjects (19 men and 17 women, mean age 37 years, SD 5 years), were included. Perceived stress at work during the past week was measured by using the Stress-Energy (SE) Questionnaire. The participants were divided into three groups based on their mean scores; Low stress, Medium stress and High stress. The participants underwent the Trier Social Stress Test (TSST) and blood samples were collected before, directly after the stress test, and after 30 min of recovery. General Linear Models were used to investigate if the Medium stress group and the High stress group differ regarding stress response compared to the Low stress group. Higher perceived stress at work was associated with attenuated DHEA-S response during acute psychosocial stress. Furthermore, the ratio between the cortisol production and the DHEA-S production during the acute stress test were higher in individuals reporting higher perceived stress at work compared to individuals reporting low perceived stress at work. There was no statistical difference in DHEA response between the groups. This study shows that prolonged stress, measured as perceived stress at work during the past week, seems to negatively affect the capacity to produce DHEA-S during acute stress. Given the protective functions of DHEA-S, attenuated DHEA-S production during acute stress may lead to higher risk for adverse effects on psychological and physiological health, particularly if stress exposure continues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reliability and validity of the de Morton Mobility Index in individuals with sub-acute stroke.

PubMed

Braun, Tobias; Marks, Detlef; Thiel, Christian; Grüneberg, Christian

2018-02-04

To establish the validity and reliability of the de Morton Mobility Index (DEMMI) in patients with sub-acute stroke. This cross-sectional study was performed in a neurological rehabilitation hospital. We assessed unidimensionality, construct validity, internal consistency reliability, inter-rater reliability, minimal detectable change and possible floor and ceiling effects of the DEMMI in adult patients with sub-acute stroke. The study included a total sample of 121 patients with sub-acute stroke. We analysed validity (n = 109) and reliability (n = 51) in two sub-samples. Rasch analysis indicated unidimensionality with an overall fit to the model (chi-square = 12.37, p = 0.577). All hypotheses on construct validity were confirmed. Internal consistency reliability (Cronbach's alpha = 0.94) and inter-rater reliability (intraclass correlation coefficient = 0.95; 95% confidence interval: 0.92-0.97) were excellent. The minimal detectable change with 90% confidence was 13 points. No floor or ceiling effects were evident. These results indicate unidimensionality, sufficient internal consistency reliability, inter-rater reliability, and construct validity of the DEMMI in patients with a sub-acute stroke. Advantages of the DEMMI in clinical application are the short administration time, no need for special equipment and interval level data. The de Morton Mobility Index, therefore, may be a useful performance-based bedside test to measure mobility in individuals with a sub-acute stroke across the whole mobility spectrum. Implications for Rehabilitation The de Morton Mobility Index (DEMMI) is an unidimensional measurement instrument of mobility in individuals with sub-acute stroke. The DEMMI has excellent internal consistency and inter-rater reliability, and sufficient construct validity. The minimal detectable change of the DEMMI with 90% confidence in stroke rehabilitation is 13 points. The lack of any floor or ceiling effects on hospital admission indicates applicability across the whole mobility spectrum of patients with sub-acute stroke.

The acute toxicity of major ion salts to Ceriodaphnia dubia: III. Mathematical models for mixture toxicity

EPA Science Inventory

Based on previous research on the acute toxicity of major ions (Na+, K+, Ca2+, Mg2+, Cl, SO42, and HCO3/CO32) to C. dubia, two mathematical models were developed for predicting the LC50 for any ion mixture, excluding those dominated by K toxicity. One model addresses a mechanism...

Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers.

PubMed

Janssen, Nicole A H; Strak, Maciej; Yang, Aileen; Hellack, Bryan; Kelly, Frank J; Kuhlbusch, Thomas A J; Harrison, Roy M; Brunekreef, Bert; Cassee, Flemming R; Steenhof, Maaike; Hoek, Gerard

2015-01-01

We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects. We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm and an urban background site. Each volunteer visited at least three sites. We conducted health measurements before exposure, 2 h after exposure and the next morning. We measured air pollution on site and characterised the OP of PM2.5 and PM10 using three a-cellular assays; dithiotreitol (OP(DTT)), electron spin resonance (OP(ESR)) and ascorbic acid depletion (OP(AA)). In single-pollutant models, all measures of OP were significantly associated with increases in fractional exhaled nitric oxide and increases in interleukin-6 in nasal lavage 2 h after exposure. These OP associations remained significant after adjustment for co-pollutants when only the four outdoor sites were included, but lost significance when measurements at the underground site were included. Other health end points including lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. We found significant associations between three a-cellular measures of OP of PM and markers of airway and nasal inflammation. However, consistency of these effects in two-pollutant models depended on how measurements at the underground site were considered. Lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Our study, therefore, provides limited support for a role of OP in predicting acute health effects of PM in healthy young adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Using nurse practitioners to implement best practice care for the elderly during hospitalization: the NICHE journey at the University of Virginia Medical Center.

PubMed

Fletcher, Kathleen; Hawkes, Polly; Williams-Rosenthal, Suzann; Mariscal, Carol S; Cox, Betty A

2007-09-01

The Nurses Improving Care to Health System (NICHE) program has provided a valuable framework for developing initiatives that address the needs of the elderly. Three NICHE models have been implemented within the University of Virginia Health System since 1992. These include the Geriatric Resource Nurse model, the Acute Care of the Elderly model, and, most recently, the Geriatric Consultation Service model. Nurse practitioners (NPs) with geriatric expertise have provided the leadership in implementing these initiatives to achieve the goal of improving geriatric care delivery within the health system. Each NP functions in a broad role that is tailored to meet the needs of the patients and staff and includes the role components of clinician, educator, team leader, and care coordinator. Sustainability and growth of NICHE is contingent upon demonstrating favorable outcomes that can be directly attributed to NICHE.

Risk determination after an acute myocardial infarction: review of 3 clinical risk prediction tools.

PubMed

Scruth, Elizabeth Ann; Page, Karen; Cheng, Eugene; Campbell, Michelle; Worrall-Carter, Linda

2012-01-01

The objective of the study was to provide comprehensive information for the clinical nurse specialist (CNS) on commonly used clinical prediction (risk assessment) tools used to estimate risk of a secondary cardiac or noncardiac event and mortality in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). The evolution and widespread adoption of primary PCI represent major advances in the treatment of acute myocardial infarction, specifically STEMI. The American College of Cardiology and the American Heart Association have recommended early risk stratification for patients presenting with acute coronary syndromes using several clinical risk scores to identify patients' mortality and secondary event risk after PCI. Clinical nurse specialists are integral to any performance improvement strategy. Their knowledge and understandings of clinical prediction tools will be essential in carrying out important assessment, identifying and managing risk in patients who have sustained a STEMI, and enhancing discharge education including counseling on medications and lifestyle changes. Over the past 2 decades, risk scores have been developed from clinical trials to facilitate risk assessment. There are several risk scores that can be used to determine in-hospital and short-term survival. This article critiques the most common tools: the Thrombolytic in Myocardial Infarction risk score, the Global Registry of Acute Coronary Events risk score, and the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications risk score. The importance of incorporating risk screening assessment tools (that are important for clinical prediction models) to guide therapeutic management of patients cannot be underestimated. The ability to forecast secondary risk after a STEMI will assist in determining which patients would require the most aggressive level of treatment and monitoring postintervention including outpatient monitoring. With an increased awareness of specialist assessment tools, the CNS can play an important role in risk prevention and ongoing cardiovascular health promotion in patients diagnosed with STEMI. Knowledge of clinical prediction tools to estimate risk for mortality and risk of secondary events after PCI for acute coronary syndromes including STEMI is essential for the CNS in assisting with improving short- and long-term outcomes and for performance improvement strategies. The risk score assessment utilizing a collaborative approach with the multidisciplinary healthcare team provides for the development of a treatment plan including any invasive intervention strategy for the patient. Copyright © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

PRN 2001-2: Acute Toxicity Data Requirements For Granular Pesticide Products, Including Those With Granular Fertilizers in the Product.

EPA Pesticide Factsheets

This PR Notice announces guidance intended to streamline the acute toxicity review and classification process for certain granular pesticide products, including those products that contain granular fertilizers.

Acute Respiratory Failure in Cardiac Transplant Recipients.

PubMed

Komurcu, Ozgur; Ozdemirkan, Aycan; Camkiran Firat, Aynur; Zeyneloglu, Pinar; Sezgin, Atilla; Pirat, Arash

2015-11-01

This study sought to evaluate the incidence, risk factors, and outcomes of acute respiratory failure in cardiac transplant recipients. Cardiac transplant recipients >15 years of age and readmitted to the intensive care unit after cardiac transplant between 2005 and 2015 were included. Thirty-nine patients were included in the final analyses. Patients with acute respiratory failure and without acute respiratory failure were compared. The most frequent causes of readmission were routine intensive care unit follow-up after endomyocardial biopsy, heart failure, sepsis, and pneumonia. Patients who were readmitted to the intensive care unit were further divided into 2 groups based on presence of acute respiratory failure. Patients' ages and body weights did not differ between groups. The groups were not different in terms of comorbidities. The admission sequential organ failure assessment scores were higher in patients with acute respiratory failure. Patients with acute respiratory failure were more likely to use bronchodilators and n-acetylcysteine before readmission. Mean peak inspiratory pressures were higher in patients in acute respiratory failure. Patients with acute respiratory failure developed sepsis more frequently and they were more likely to have hypotension. Patients with acute respiratory failure had higher values of serum creatinine before admission to intensive care unit and in the first day of intensive care unit. Patients with acute respiratory failure had more frequent bilateral opacities on chest radiographs and positive blood and urine cultures. Duration of intensive care unit and hospital stays were not statistically different between groups. Mortality in patients with acute respiratory failure was 76.5% compared with 0% in patients without acute respiratory failure. A significant number of cardiac transplant recipients were readmitted to the intensive care unit. Patients presenting with acute respiratory failure on readmission more frequently developed sepsis and hypotension, suggesting a poorer prognosis.

Violence Among Men and Women in Substance Use Disorder Treatment: A Multi-level Event-based Analysis

PubMed Central

Chermack, Stephen T.; Grogan-Kaylor, Andy; Perron, Brian E.; Murray, Regan L.; De Chavez, Peter; Walton, Maureen A.

2010-01-01

Background This study examined associations between acute alcohol and drug use and violence towards others in conflict incidents (overall, partner, and non-partner conflict incidents) by men and women recruited from substance use disorder (SUD) treatment. Methods Semi-structured interviews were used to obtain details about interpersonal conflict incidents (substance use, whether specific conflicts were with intimate partners or non-partners) in the 180 days pre-treatment. Participants for this study were selected for screening positive for past-year violence (N = 160; 77% men, 23% women). Results Multilevel multinomial regression models showed that after adjusting for clustering within individual participants, the most consistent predictors of violence across models were acute cocaine use (significant for overall, intimate partner and non-partner models), acute heavy alcohol use (significant for overall and non-partner models), and male gender (significant in all models). Conclusions This study was the first to explicitly examine the role of acute alcohol and drug use across overall, partner and non-partner conflict incidents. Consistent with prior studies using a variety of methodologies, alcohol, cocaine use and male gender were most consistently and positively related to violence severity (e.g., resulting in injury). The results provide important and novel event-level information regarding the relationship between acute alcohol and specific drug use and the severity of violence in interpersonal conflict incidents. PMID:20667666

The first dedicated life sciences mission - Spacelab 4

NASA Astrophysics Data System (ADS)

Cramer, D. R.; Reid, D. H.; Klein, H. P.

Spacelab is a large versatile laboratory carried in the bay of the Shuttle Orbiter. The first Spacelab mission dedicated entirely to Life Sciences is known as Spacelab 4. It is scheduled for launch in late 1985 and will remain aloft for seven days. This payload consists of 25 tentatively selected investigations combined into a comprehensive integrated exploration of the effects of acute weightlessness on living systems. An emphasis is placed on studying physiological changes that have been previously observed in manned space flight. This payload has complementary designs in the human and animal investigations in order to validate animal models of human physiology in weightlessness. The experimental subjects include humans, squirrel monkeys, laboratory rats, several species of plants, and frog eggs. The primary scientific objectives include study of the acute cephalic fluid shift, cardiovascular adaptation to weightlessness, including postflight reductions in orthostatic tolerance and exercise capacity, and changes in vestibular function, including space motion sickness, associated with weightlessness. Secondary scientific objectives include the study of red cell mass reduction, negative nitrogen balance, altered calcium metabolism, suppressed in vitro lymphocyte reactivity, gravitropism and photropism in plants, and fertilization and early development in frog eggs. The rationale behind this payload, the selection process, and details of the individual investigations are presented in this paper.