State-Level CPR Education Legislation Associated With Higher Survival After Out-Of-Hospital Cardiac Arrest in Older Adults

Introduction: State-level legislation requiring CPR education prior to high school graduation is associated with an increased likelihood of community-level CPR training. CPR Legislation has also been shown to be associated with increased bystander CPR. We hypothesized that states with CPR Legislation would be associated with higher survival following out-of-hospital cardiac arrest (OHCA). Methods: Utilizing 2014 Medicare Claims data for emergency department visits and inpatient stays, we identified OHCA via ICD-9-CM code. CPR Legislation data was collected through online statute review. Exposure to CPR Legislation was assessed using the patient state of residence. All disposition categories were considered survival to discharge except for death/hospice. Associations between categorical variables were assessed by chi-squared test. Multiple logistic regression was used to calculate the odds ratio associated with OHCA survival and CPR Legislation, controlling for patient age and sex. Results: States that passed CPR Legislation in 2013 had the highest survival compared to states with earlier passage or no CPR Legislation (22.2% vs 20.6% vs. 21.8%, respectively, p \u3c 0.001). Results of the multiple logistic regression showed CPR Legislation passed in 2013 was associated with a 12% increase in the odds of survival to discharge compared to states with CPR Legislation prior to 2013 (OR: 1.12, p \u3c0.001). Discussion: States with CPR Legislation passed in 2013 were associated with higher survival to discharge and discharge to home, compared to earlier adopters and states with no legislation. Further work is needed to assess the mechanisms underlying this relationship

Inpatient hospital performance is associated with post-discharge sepsis mortality.

BACKGROUND: Post-discharge deaths are common in patients hospitalized for sepsis, but the drivers of post-discharge deaths are unclear. The objective of this study was to test the hypothesis that hospitals with high risk-adjusted inpatient sepsis mortality also have high post-discharge mortality, readmissions, and discharge to nursing homes. METHODS: Retrospective cohort study of age-qualifying Medicare beneficiaries with sepsis hospitalization between January 2013 and December 2014. Hospital survivors were followed for 180-days post-discharge, and mortality, readmissions, and new admission to skilled nursing facility were measured. Inpatient hospital-specific sepsis risk-adjusted mortality ratio (observed: expected) was the primary exposure. RESULTS: A total of 830,721 patients in the cohort were hospitalized for sepsis, with inpatient mortality of 20% and 90-day mortality of 48%. Higher hospital-specific sepsis risk-adjusted mortality was associated with increased 90-day post-discharge mortality (aOR 1.03 per each 0.1 increase in hospital inpatient O:E ratio, 95% CI 1.03-1.04). Higher inpatient risk adjusted mortality was also associated with increased probability of being discharged to a nursing facility (aOR 1.03, 95% CI 1.02-1.03) and 90-day readmissions (aOR 1.03, 95% CI 1.02-1.03). CONCLUSIONS: Hospitals with the highest risk-adjusted sepsis inpatient mortality also have higher post-discharge mortality and increased readmissions, suggesting that post-discharge complications are a modifiable risk that may be affected during inpatient care. Future work will seek to elucidate inpatient and healthcare practices that can reduce sepsis post-discharge complications

Recruitment for a Hospital-Based Pragmatic Clinical Trial using Volunteer Nurses and Students

BACKGROUND/AIMS: Recruitment of subjects is critical to the success of any clinical trial, but achieving this goal can be a challenging endeavor. Volunteer nurse and student enrollers are potentially an important source of recruiters for hospital-based trials; however, little is known of either the efficacy or cost of these types of enrollers. We assessed volunteer clinical nurses and health science students in their rates of enrolling family members in a hospital-based, pragmatic clinical trial of cardiopulmonary resuscitation education, and their ability to achieve target recruitment goals. We hypothesized that students would have a higher enrollment rate and are more cost-effective compared to nurses. METHODS: Volunteer nurses and student enrollers were recruited from eight institutions. Participating nurses were primarily bedside nurses or nurse educators while students were pre-medical, pre-nursing, and pre-health students at local universities. We recorded the frequency of enrollees recruited into the clinical trial by each enroller. Enrollers\u27 impressions of recruitment were assessed using mixed-methods surveys. Cost was estimated based on enrollment data. Overall enrollment data were analyzed using descriptive statistics and generalized estimating equations. RESULTS: From February 2012 to November 2014, 260 hospital personnel (167 nurses and 93 students) enrolled 1493 cardiac patients\u27 family members, achieving target recruitment goals. Of those recruited, 822 (55%) were by nurses, while 671 (45%) were by students. Overall, students enrolled 5.44 (95% confidence interval (CI): 2.88, 10.27) more subjects per month than nurses (p \u3c 0.01). After consenting to participate in recruitment, students had a 2.85 (95% CI: 1.09, 7.43) increased chance of enrolling at least one family member (p = 0.03). Among those who enrolled at least one subject, nurses enrolled a mean of 0.51(95% CI: 0.42, 0.59) subjects monthly, while students enrolled 1.63 (95% CI: 1.37, 1.90) per month (p \u3c 0.01). Of 198 surveyed hospital personnel (127 nurses, 71 students), 168/198 (85%) felt confident conducting enrollment. The variable cost per enrollee recruited was $25.38 per subject for nurses and$23.30 per subject for students. CONCLUSIONS: Overall, volunteer students enrolled more subjects per month at a lower cost than nurses. This work suggests that recruitment goals for a pragmatic clinical trial can be successfully obtained using both nurses and students

Degenerate recognition of MHC class I molecules with Bw4 and Bw6 motifs by a killer cell Ig-like receptor 3DL expressed by macaque NK cells

The killer cell immunoglobulin-like receptors (KIRs) expressed on the surface of natural killer (NK) cells recognize specific major histocompatibility complex class I (MHC-I) molecules and regulate NK cell activities against pathogen-infected cells and neoplasia. In human immunodeficiency virus (HIV) infection, survival is linked to host KIR and MHC-I genotypes. In the simian immunodeficiency virus (SIV) macaque model, however, the role of NK cells is unclear due to the lack of information on KIR-MHC interactions. Here, we describe the first characterization of a KIR-MHC interaction in pig-tailed macaques (Macaca nemestrina). Initially, we identified three distinct subsets of macaque NK cells that stained ex vivo with macaque MHC-I tetramers loaded with SIV peptides. We then cloned cDNAs corresponding to 15 distinct KIR3D alleles. One of these, KIR049-4, was an inhibitory KIR3DL that bound MHC-I tetramers and prevented activation, degranulation and cytokine production by macaque NK cells after engagement with specific MHC-I molecules on the surface of target cells. Furthermore, KIR049-4 recognized a broad range of MHC-I molecules carrying not only the Bw4 motif but also Bw6 and non-Bw4/Bw6 motifs. This degenerate, yet peptide-dependent, MHC reactivity differs markedly from the fine specificity of human KIRs

Spo0A∼P Imposes a Temporal Gate for the Bimodal Expression of Competence in Bacillus subtilis

ComK transcriptionally controls competence for the uptake of transforming DNA in Bacillus subtilis. Only 10%–20% of the cells in a clonal population are randomly selected for competence. Because ComK activates its own promoter, cells exceeding a threshold amount of ComK trigger a positive feedback loop, transitioning to the competence ON state. The transition rate increases to a maximum during the approach to stationary phase and then decreases, with most cells remaining OFF. The average basal rate of comK transcription increases transiently, defining a window of opportunity for transitions and accounting for the heterogeneity of competent populations. We show that as the concentration of the response regulator Spo0A∼P increases during the entry to stationary phase it first induces comK promoter activity and then represses it by direct binding. Spo0A∼P activates by antagonizing the repressor, Rok. This amplifies an inherent increase in basal level comK promoter activity that takes place during the approach to stationary phase and is a general feature of core promoters, serving to couple the probability of competence transitions to growth rate. Competence transitions are thus regulated by growth rate and temporally controlled by the complex mechanisms that govern the formation of Spo0A∼P. On the level of individual cells, the fate-determining noise for competence is intrinsic to the comK promoter. This overall mechanism has been stochastically simulated and shown to be plausible. Thus, a deterministic mechanism modulates an inherently stochastic process

Distinct Expression/Function of Potassium and Chloride Channels Contributes to the Diverse Volume Regulation in Cortical Astrocytes of GFAP/EGFP Mice

Recently, we have identified two astrocytic subpopulations in the cortex of GFAP-EGFP mice, in which the astrocytes are visualized by the enhanced green–fluorescent protein (EGFP) under the control of the human glial fibrillary acidic protein (GFAP) promotor. These astrocytic subpopulations, termed high response- (HR-) and low response- (LR-) astrocytes, differed in the extent of their swelling during oxygen-glucose deprivation (OGD). In the present study we focused on identifying the ion channels or transporters that might underlie the different capabilities of these two astrocytic subpopulations to regulate their volume during OGD. Using three-dimensional confocal morphometry, which enables quantification of the total astrocytic volume, the effects of selected inhibitors of K+ and Cl− channels/transporters or glutamate transporters on astrocyte volume changes were determined during 20 minute-OGD in situ. The inhibition of volume regulated anion channels (VRACs) and two-pore domain potassium channels (K2P) highlighted their distinct contributions to volume regulation in HR-/LR-astrocytes. While the inhibition of VRACs or K2P channels revealed their contribution to the swelling of HR-astrocytes, in LR-astrocytes they were both involved in anion/K+ effluxes. Additionally, the inhibition of Na+-K+-Cl− co-transporters in HR-astrocytes led to a reduction of cell swelling, but it had no effect on LR-astrocyte volume. Moreover, employing real-time single-cell quantitative polymerase chain reaction (PCR), we characterized the expression profiles of EGFP-positive astrocytes with a focus on those ion channels and transporters participating in astrocyte swelling and volume regulation. The PCR data revealed the existence of two astrocytic subpopulations markedly differing in their gene expression levels for inwardly rectifying K+ channels (Kir4.1), K2P channels (TREK-1 and TWIK-1) and Cl− channels (ClC2). Thus, we propose that the diverse volume changes displayed by cortical astrocytes during OGD mainly result from their distinct expression patterns of ClC2 and K2P channels

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution

利用重正化群方法推导非线性Reynolds应力模型

近年来,Rubinstein和Barton利用Yakhot和Orszag湍流重正化群方法推导非线性Reynolds应力模型,但是他们分析计算过程中存在着一些不自洽的地方.文中利用重正化群方法,对Reynolds应力的数学表达式作二阶微扰展开,从理论上推导得到非线性Reynolds应力模型,其数学形式与从量纲分析和数学物理性质的合理性讨论得到的通用模型形式完全相同,另外从理论上计算了各待定湍流常数

Impact of adrenaline dose and timing on out-of-hospital cardiac arrest survival and neurological outcomes.

STUDY OBJECTIVE: The 2015 ILCOR Advanced Cardiovascular Life Support Guidelines recommend intravenous adrenaline (epinephrine) as a crucial pharmacologic treatment during cardiac arrest resuscitation. Some recent observational studies and clinical trials have questioned the efficacy of its use and suggested possible deleterious effects on overall survival and long-term outcomes. This study aimed to describe the association between time and dose of adrenaline on return of spontaneous circulation (ROSC) and neurologic function. METHODS: We performed a retrospective analysis of the Penn Alliance for Therapeutic Hypothermia (PATH) data registry. The timing of the first dose of adrenaline and the total dose of adrenaline during cardiac arrests was compared between survivors to discharge and non-survivors for arrests lasting greater than 10 min. RESULTS: The registry contained 5594 patients. After excluding patients with an in-hospital cardiac arrest, a non-shockable rhythm, or no adrenaline administration, 1826 were included in the final analysis. Survivors to discharge received adrenaline sooner (median 5.0 vs. 7.0 min, p = 0.022) and required a lower total dose than non-survivors (2.0 vs. 3.0 mg, p \u3c 0.001). For survivors, there was no significant association between the time to first adrenaline dose and favorable neurological outcome as measured by Cerebral Performance Category (CPC). Among survivors, those that received less than 2 mg of adrenaline had a more favorable neurologic outcome than those administered \u3e 3 mg. (CPC 1-2 16.6% vs. 12.5%, p = 0.004). CONCLUSION: Early adrenaline administration is associated with a higher percentage of survival to discharge but not associated with favorable neurological outcome. Those patients with a favorable neurologic outcome received a lower total adrenaline dose prior to ROSC