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Background Do Not Resuscitate (DNR) orders are intended to safeguard patients' autonomy and prevent unwanted resuscitative care. However, DNR orders may be miscommunicated between health care providers, leading to errors honoring patient wishes during cardiac arrest events. This project focused on improving accuracy of DNR ordering processes for an academic, tertiary care hospital. Intervention We describe a performance improvement process and outcomes for implementation of an inpatient electronic ordering system that included an automated, decentralized printing process for resuscitation status armbands. Specific phases of this project involved: (a) identification of common factors contributing to errors honoring patients‘ resuscitation wishes, (b) design of an electronic ordering process, (c) design and integration of a new DNR armband and (d) evaluation of the impact of changes on communication accuracy. The primary outcome was percentage of patients with incorrect designation of resuscitation status on armbands compared to the active resuscitation order in the electronic medical record. Results After implementation of an electronic ordering process we identified that 37/196 (19%) patients had an armband that did not reflect their documented wishes versus 2/103 (2%) after integration of automated armband printing into the process (p<0.001). No armband discrepancies were found after the first two weeks of post-implementation audits. Conclusions Design and implementation of an electronic ordering and armband labeling process reduced discrepancies between patient wishes and the armband labeling of the patient's desired DNR status. It is anticipated that these improvements will reduce the risk of adverse outcomes, and better align clinical processes with patient wishes.

AbstractTo address the pending public health crisis due to Alzheimer's disease (AD) and related neurodegenerative disorders, the Marian S. Ware Alzheimer Program at the University of Pennsylvania held a meeting entitled “State of the Science Conference on the Advancement of Alzheimer's Diagnosis, Treatment and Care,” on June 21‐22, 2012. The meeting comprised four workgroups focusing on Biomarkers; Clinical Care and Health Services Research; Drug Development; and Health Economics, Policy, and Ethics. The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article.

A Fine Balance Intellectual and neurological disabilities can arise from diverse developmental aberrations. Novarino et al. (p. 394 , published online 6 September; see the Perspective by Beaudet ) have now determined the genetic basis for one such disorder for a small group of patients. Exome sequencing led to identification of mutations in a kinase BCKDK ( Branched Chain Ketoacid Dehydrogenase Kinase ) that regulates metabolism of branched-chain amino acids such as valine, leucine, and isoleucine. Mice with homozygous mutations in the BCKDK gene showed developmental and neurological abnormalities resembling those in certain mouse autism models. Analysis of transport mechanisms responsible for carrying amino acids across the blood-brain barrier revealed competition between the branched-chain amino acids and large neutral amino acids. Nutritional supplementation with extra branched-chain amino acids in the diet of mice carrying homozygous mutations in the BCKDK gene normalized their phenotype.

Introduction Acute lung injury (ALI) is a devastating condition that places a heavy burden on public health resources. Although the need for effective ALI prevention strategies is increasingly recognised, no effective preventative strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to test whether aspirin (ASA) could prevent and/or mitigate the development of ALI. Methods and analysis LIPS-A is a multicentre, double-blind, randomised clinical trial testing the hypothesis that the early administration of ASA will result in a reduced incidence of ALI in adult patients at high risk. This investigation will enrol 400 study participants from 14 hospitals across the USA. Conditional logistic regression will be used to test the primary hypothesis that early ASA administration will decrease the incidence of ALI. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approval of both the protocol and informed consent documents were also obtained from the institutional review board of each participating institution prior to enrolling study participants at the respective site. In addition to providing important clinical and mechanistic information, this investigation will inform the scientific merit and feasibility of a phase III trial on ASA as an ALI prevention agent. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to Pub Med Central in accordance with the National Institute of Health Public Access Policy.

AbstractSurprisingly, the role(s) of eosinophils in health and disease is often summarized by clinicians and basic research scientists as a pervasive consensus opinion first learned in medical/graduate school. Eosinophils are rare white blood cells whose activities are primarily destructive and are only relevant in parasitic infections and asthma. However, is this consensus correct? This review argues that the wealth of available studies investigating the role(s) of eosinophils in both health and disease demonstrates that the activities of these granulocytes are far more expansive and complex than previously appreciated. In turn, this greater understanding has led to the realization that eosinophils have significant contributory roles in a wide range of diseases. Furthermore, published studies even implicate eosinophil-mediated activities in otherwise healthy persons. We suggest that the collective reports in the literature showing a role for eosinophils in an ever-increasing number of novel settings highlight the true complexity and importance of this granulocyte. Indeed, discussions of eosinophils are no longer simple and more often than not now begin with the question/statement “Did you know …?”

ABSTRACT Productive replication of human immunodeficiency virus type 1 (HIV-1) occurs efficiently only in humans. The posttranscriptional stages of the HIV-1 life cycle proceed poorly in mouse cells, with a resulting defect in viral assembly and release. Previous work has shown that the presence of human chromosome 2 increases HIV-1 production in mouse cells. Recent studies have shown that human chromosome region maintenance 1 (hCRM1) stimulates Gag release from rodent cells. Here we report that expressions of hCRM1 in murine cells resulted in marked increases in the production of infectious HIV-1 and feline immunodeficiency virus (FIV). HIV-1 production was also increased by hSRp40, and a combination of hCRM1 and hSRp40 resulted in a more-than-additive effect on HIV-1 release. In contrast, the overexpression of mouse CRM1 (mCRM1) minimally affected HIV-1 and FIV production and did not antagonize hCRM1. In the presence of hCRM1 there were large increases in the amounts of released capsid, which paralleled the increases in the infectious titers. Consistent with this finding, the ratios of unspliced to spliced HIV-1 mRNAs in mouse cells expressing hCRM1 and SRp40 became similar to those of human cells. Furthermore, imaging of intron-containing FIV RNA showed that hCRM1 increased RNA export to the cytoplasm.By testing chimeras between mCRM1 and hCRM1 and comparing those sequences to feline CRM1, we mapped the functional domain to HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A, and the yeast kinase TOR1) repeats 4A to 9A and a triple point mutant in repeat 9A, which showed a loss of function. Structural analysis suggested that this region of hCRM1 may serve as a binding site for viral or cellular factors to facilitate lentiviral RNA nuclear export.

Background Higher mortality for patients with aneurysmal subarachnoid haemorrhage has been reported. Aims In families with intracranial aneurysms, we sought to determine whether mortality among subjects with intracranial aneurysm (affected) was higher and related to rupture, compared with unaffected family members. Methods Subjects enrolled in the Familial Intracranial Aneurysm protocol were contacted yearly and their status was obtained. If reported to be deceased, the cause of death was verified by available records. A Cox proportional hazards model was utilized to compare mortality rates. Results Of the 2794 subjects, 1073 were affected and 1721 were unaffected. There were 8525 person-years of follow-up (mean 3·05 ± 1·73 years) and 85 deaths. Age at study entry for the affected (58·4 ±11·9 years) was significantly older ( P < 0·0001) than for the unaffected (52·2 ± 16·1). After adjusting for age, the overall mortality rate for the affected subjects was not significantly different from that for the unaffected (Rate Ratio [RR] 1·26, 95% confidence interval 0·82–1·93, P = 0·292). There was a strong effect modification due to age. The mortality rate ratio of the affected to the unaffected who were ≤60 years of age was RR = 3·48 (95% confidence interval: 1·59–7·63, P = 0·002), the rate for the affected subjects who were ≥60 was less than the rate for the unaffected (RR = 0·69, 95% confidence interval: 0·404–1·19, P = 0·178). The affected who had ruptures had 2·62 times the mortality rate as those without ruptures (95% confidence interval 1·43–4·80, P = 0·002). Conclusion The overall mortality was similar for the affected and unaffected subjects in this cohort. Among the affected only, those with ruptured intracranial aneurysm had a higher mortality rate than those without ruptured.