The Complexity of Determining Whether a Nursing Home Transfer Is Avoidable at Time of Transfer

Objectives To describe the relationship between nursing facility resident risk conditions and signs and symptoms at time of acute transfer and diagnosis of conditions associated with potentially avoidable acute transfers (pneumonia, urinary tract infection, congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) or asthma, dehydration, pressure sores). Design As part of a demonstration project to reduce potentially avoidable hospital transfers, Optimizing Patient Transfers, Impacting Medical Quality, Improving Symptoms: Transforming Institutional Care (OPTIMISTIC) project clinical staff collected data on residents who transferred to the emergency department (ED) or hospital. Cross‐tabulations were used to identify associations between risk conditions or symptoms and hospital diagnoses or death. Mixed‐effects logistic regression models were used to describe the significance of risk conditions, signs, or symptoms as predictors of potentially avoidable hospital diagnoses or death. Setting Indiana nursing facilities (N=19). Participants Long‐stay nursing facility residents (N=1,174), who experienced 1,931 acute transfers from November 2014 to July 2016. Measurements Participant symptoms, transfers, risk factors, and hospital diagnoses. Results We found that 44% of acute transfers were associated with 1 of 6 potentially avoidable diagnoses. Symptoms before transfer did not discriminate well among hospital diagnoses. Symptoms mapped into multiple diagnoses and most hospital diagnoses had multiple associated symptoms. For example, more than two‐thirds of acute transfers of residents with a history of CHF and COPD were for reasons other than exacerbations of those two conditions. Conclusion Although it is widely recognized that many transfers of nursing facility residents are potentially avoidable, determining “avoidability” at time of transfer is complex. Symptoms and risk conditions were only weakly predictive of hospital diagnoses

Complement Inhibition as a Proposed Neuroprotective Strategy following Cardiac Arrest

Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R) injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA

Complement Inhibition Promotes Endogenous Neurogenesis and Sustained Anti-Inflammatory Neuroprotection following Reperfused Stroke

The restoration of blood-flow following cerebral ischemia incites a series of deleterious cascades that exacerbate neuronal injury. Pharmacologic inhibition of the C3a-receptor ameliorates cerebral injury by attenuating post-ischemic inflammation. Recent reports also implicate C3a in the modulation of tissue repair, suggesting that complement may influence both injury and recovery at later post-ischemic time-points.To evaluate the effect of C3a-receptor antagonism on post-ischemic neurogenesis and neurological outcome in the subacute period of stroke, transient focal cerebral ischemia was induced in adult male C57BL/6 mice treated with multiple regimens of a C3a receptor antagonist (C3aRA).Low-dose C3aRA administration during the acute phase of stroke promotes neuroblast proliferation in the subventricular zone at 7 days. Additionally, the C3a receptor is expressed on T-lymphocytes within the ischemic territory at 7 days, and this cellular infiltrate is abrogated by C3aRA administration. Finally, C3aRA treatment confers robust histologic and functional neuroprotection at this delayed time-point.Targeted complement inhibition through low-dose antagonism of the C3a receptor promotes post-ischemic neuroblast proliferation in the SVZ. Furthermore, C3aRA administration suppresses T-lymphocyte infiltration and improves delayed functional and histologic outcome following reperfused stroke. Post-ischemic complement activation may be pharmacologically manipulated to yield an effective therapy for stroke

Pharmacotherapy of cerebral ischemia

BACKGROUND: Ischemic stroke remains one of the leading causes of death and disability in the developed world. Despite many promising preclinical results, the only pharmacologic treatments proven effective in improving clinical outcome following ischemic stroke until now are administration of aspirin and acute thrombolysis using tissue-plasminogen activator. OBJECTIVE: To review currently approved pharmacologic therapies as well as promising future treatment strategies for acute ischemic stroke. METHODS: We performed an exhaustive PubMed search for articles published from 1950 through 2009 describing pharmacotherapy of acute ischemic stroke, focusing on agents that are currently in Phase III trials or approved for clinical use. Following this review, we present our interpretation of the existing literature and our vision of the future of pharmacotherapy for ischemic stroke. RESULTS/CONCLUSIONS: Since the clinical success of the first intravenous thrombolytic, many studies have sought to further characterize the ideal patient population and to extend the therapeutic time window for pharmacologic thrombolysis. Additionally, despite the many failures of neuroprotective trials, several promising agents are currently undergoing Phase III investigation. With the advent of interventional techniques enabling local delivery of therapeutics into the region of the thrombus, the future of pharmacotherapy for ischemic stroke will probably include a combination of interventional techniques and pharmacotherapy

Complement inhibition as a proposed neuroprotective strategy following cardiac arrest

Out-of-hospital cardiac arrest (OHCA) is a devastating disease process with neurological injury accounting for a disproportionate amount of the morbidity and mortality following return of spontaneous circulation. A dearth of effective treatment strategies exists for global cerebral ischemia-reperfusion (GCI/R) injury following successful resuscitation from OHCA. Emerging preclinical as well as recent human clinical evidence suggests that activation of the complement cascade plays a critical role in the pathogenesis of GCI/R injury following OHCA. In addition, it is well established that complement inhibition improves outcome in both global and focal models of brain ischemia. Due to the profound impact of GCI/R injury following OHCA, and the relative lack of effective neuroprotective strategies for this pathologic process, complement inhibition provides an exciting opportunity to augment existing treatments to improve patient outcomes. To this end, this paper will explore the pathophysiology of complement-mediated GCI/R injury following OHCA

The complement cascade as a therapeutic target in intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is the second most common and deadliest form of stroke. Currently, no pharmacologic treatment strategies exist for this devastating disease. Following the initial mechanical injury suffered at hemorrhage onset, secondary brain injury proceeds through both direct cellular injury and inflammatory cascades, which trigger infiltration of granulocytes and monocytes, activation of microglia, and disruption of the blood-brain barrier with resulting cerebral edema. The complement cascade has been shown to play a central role in the pathogenesis of secondary injury following ICH, although the specific mechanisms responsible for the proximal activation of complement remain incompletely understood. Cerebral injury following cleavage of complement component 3 (C3) proceeds through parallel but interrelated pathways of anaphylatoxin-mediated inflammation and direct toxicity secondary to membrane attack complex-driven erythrocyte lysis. Complement activation also likely plays an important physiologic role in recovery following ICH. As such, a detailed understanding of the variation in functional effects of complement activation over time is critical to exploiting this target as an exciting translational strategy for intracerebral hemorrhage

Epidemiology of aneurysmal subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage (aSAH) is a form of hemorrhagic stroke that affects up to 30,000 individuals per year in the United States. The incidence of aSAH has been shown to be associated with numerous nonmodifiable (age, gender, ethnicity, family history, aneurysm location, size) and modifiable (hypertension, body mass index, tobacco and illicit drug use) risk factors. Although early repair of ruptured aneurysms and aggressive postoperative management has improved overall outcomes, it remains a devastating disease, with mortality approaching 50% and less than 60% of survivors returning to functional independence. As treatment modalities change and the percentage of minority and elderly populations increase, it is critical to maintain an up-to-date understanding of the epidemiology of SAH

Assessing biodegradation potential of PAHs in complex multi-contaminant matrices.

This study sought to extend validation of a cyclodextrin based extraction method for the assessment of PAH-biodegradation potential to complex multi-contaminant matrices. To this end, four reference materials (RMs) were produced by blending, in different proportions, soils impacted with diesel, lubricating oil and spent oxide. These reference materials had modest Sigma PAH (16 US EPA) concentrations that ranged from 5.6 +/- 0.5 to 44.4 +/- 4.5 mg kg(-1). However, extractable petroleum hydrocarbon (EPH) concentrations were comparatively high (up to 2520 +/- 204 mg kg-1). To complement these RMs, two further soils from a municipal gas plant (MGP) with highly elevated concentration of PAHs ranging from 877 +/- 52 to 2620 +/- 344 mg kg(-1) were also tested. Results showed, regardless of matrix complexity, that PAH biodegradation within the four RM substrates, and two MGP soils correlated well with biodegradation predicted by hydroxypropyl-5-cyclodextrin (HPCD) extraction. (C) 2008 Elsevier Ltd. All rights reserved

Intracranial infectious aneurysms: a comprehensive review

Intracranial infectious aneurysms, or mycotic aneurysms, are rare infectious cerebrovascular lesions which arise through microbial infection of the cerebral arterial wall. Due to the rarity of these lesions, the variability in their clinical presentations, and the lack of population-based epidemiological data, there is no widely accepted management methodology. We undertook a comprehensive literature search using the OVID gateway of the MEDLINE database (1950-2009) using the following keywords (singly and in combination): infectious, mycotic, cerebral aneurysm, and intracranial aneurysm. We identified 27 published clinical series describing a total of 287 patients in the English literature that presented demographic and clinical data regarding presentation, treatment, and outcome of patients with mycotic aneurysms. We then synthesized the available data into a combined cohort to more closely estimate the true demographic and clinical characteristics of this disease. We follow by presenting a comprehensive review of mycotic aneurysms, highlighting current treatment paradigms. The literature supports the administration of antibiotics in conjunction with surgical or endovascular intervention depending on the character and location of the aneurysm, as well as the clinical status of the patient. Mycotic aneurysms comprise an important subtype of potentially life-threatening cerebrovascular lesions, and further prospective studies are warranted to define outcome following both conservative and surgical or endovascular treatment