Early Convalescent Plasma for High-Risk Outpatients with Covid-19.

BACKGROUND: Early administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19. METHODS: In this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause. RESULTS: A total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups. CONCLUSIONS: The administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.).

Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus.

BACKGROUND: Neuropsychiatric lupus (NPSLE) describes the cognitive, memory, and affective emotional burdens faced by many lupus patients. While NPSLE's pathogenesis has not been fully elucidated, clinical imaging studies and cerebrospinal fluid (CSF) findings, namely elevated interleukin-6 (IL-6) levels, point to ongoing neuroinflammation in affected patients. Not only linked to systemic autoimmunity, IL-6 can also activate neurotoxic glial cells the brain. A prior pre-clinical study demonstrated that IL-6 can acutely induce a loss of sucrose preference; the present study sought to assess the necessity of chronic IL-6 exposure in the NPSLE-like disease of MRL/lpr lupus mice. METHODS: We quantified 1308 proteins in individual serum or pooled CSF samples from MRL/lpr and control MRL/mpj mice using protein microarrays. Serum IL-6 levels were plotted against characteristic NPSLE neurobehavioral deficits. Next, IL-6 knockout MRL/lpr (IL-6 KO; n = 15) and IL-6 wildtype MRL/lpr mice (IL-6 WT; n = 15) underwent behavioral testing, focusing on murine correlates of learning and memory deficits, depression, and anxiety. Using qPCR, we quantified the expression of inflammatory genes in the cortex and hippocampus of MRL/lpr IL-6 KO and WT mice. Immunofluorescent staining was performed to quantify numbers of microglia (Iba1 +) and astrocytes (GFAP +) in multiple cortical regions, the hippocampus, and the amygdala. RESULTS: MRL/lpr CSF analyses revealed increases in IL-17, MCP-1, TNF-α, and IL-6 (a priori p-value < 0.1). Serum levels of IL-6 correlated with learning and memory performance (R2 = 0.58; p = 0.03), but not motivated behavior, in MRL/lpr mice. Compared to MRL/lpr IL-6 WT, IL-6 KO mice exhibited improved novelty preference on object placement (45.4% vs 60.2%, p < 0.0001) and object recognition (48.9% vs 67.9%, p = 0.002) but equivalent performance in tests for anxiety-like disease and depression-like behavior. IL-6 KO mice displayed decreased cortical expression of aif1 (microglia; p = 0.049) and gfap (astrocytes; p = 0.044). Correspondingly, IL-6 KO mice exhibited decreased density of GFAP + cells compared to IL-6 WT in the entorhinal cortex (89 vs 148 cells/mm2, p = 0.037), an area vital to memory. CONCLUSIONS: The inflammatory composition of MRL/lpr CSF resembles that of human NPSLE patients. Increased in the CNS, IL-6 is necessary to the development of learning and memory deficits in the MRL/lpr model of NPSLE. Furthermore, the stimulation of entorhinal astrocytosis appears to be a key mechanism by which IL-6 promotes these behavioral deficits.

Novel biomarker discovery through comprehensive proteomic analysis of lupus mouse serum.

OBJECTIVES: The difficulty of monitoring organ-specific pathology in systemic lupus erythematosus (SLE) often complicates disease prognostication and treatment. Improved non-invasive biomarkers of active organ pathology, particularly lupus nephritis, would improve patient care. We sought to validate and apply a novel strategy to generate the first comprehensive serum proteome of a lupus mouse model and identify mechanism-linked lupus biomarker candidates for subsequent clinical investigation. METHODS: Serum levels of 1308 diverse proteins were measured in eight adult female MRL/lpr lupus mice and eight control MRL/mpj mice. ELISA validation confirmed fold increases. Protein enrichment analysis provided biological relevance to findings. Individual protein levels were correlated with measures of lymphoproliferative, humoral, and renal disease. RESULTS: Four hundred and six proteins were increased in MRL/lpr serum, including proteins increased in human SLE such as VCAM-1, L-selectin, TNFRI/II, TWEAK, CXCL13, MCP-1, IP-10, IL-10, and TARC. Newly validated proteins included IL-6, IL-17, and MDC. Results of pathway enrichment analysis, which revealed enhancement of cytokine signaling and immune cell migration, reinforced the similarity of the MRL/lpr disease to human pathology. Fifty-two proteins positively correlated with at least one measure of lupus-like disease. TECK, TSLP, PDGFR-alpha, and MDC were identified as novel candidate biomarkers of renal disease. CONCLUSIONS: We successfully validated a novel serum proteomic screening strategy in a spontaneous murine lupus model that highlighted potential new biomarkers. Importantly, we generated a comprehensive snapshot of the serum proteome which will enable identification of other candidates and serve as a reference for future mechanistic and therapeutic studies in lupus.

Changes in opioid prescribing and prescription drug monitoring program utilization following electronic health record integration-Massachusetts, 2018.

OBJECTIVE: In this study, we explored key prescription drug monitoring program-related outcomes among clinicians from a broad cohort of Massachusetts healthcare facilities following prescription drug monitoring program (PDMP) and electronic health record (EHR) data integration. METHODS: Outcomes included seven-day rolling averages of opioids prescribed, morphine milligram equivalents (MMEs) prescribed, and PDMP queries. We employed a longitudinal study design to analyze PDMP data over a 15-month study period which allowed for six and a half months of pre- and post-integration observations surrounding a two-month integration period. We used longitudinal mixed effects models to examine the effect of EHR integration on each of the key outcomes. RESULTS: Following EHR integration, PDMP queries increased both through the web-based portal and in total (0.037, [95% CI = 0.017, 0.057] and 0.056, [95% CI = 0.035, 0.077]). Both measures of clinician opioid prescribing declined throughout the study period; however, no significant effect following EHR integration was observed. These results were consistent when our analysis was applied to a subset consisting only of continuous PDMP users. CONCLUSIONS: Our results support EHR integration contributing to PDMP utilization by clinicians but do not support changes in opioid prescribing behavior.

Progress and unmet needs in understanding fundamental mechanisms of autoimmunity.

The rising incidence of autoimmune diseases is straining the healthcare system's capacity to care for patients with autoimmunity. To further compound this growing crisis, this rise occurs at a time when virulent infectious diseases exacerbate pre-existing conditions. Despite some novel targeted therapies introduced over the preceding decades, current treatment strategies must often fall back on non-specific immunosuppression, inflicting its own toll on patient morbidity. To improve patient care, we must re-double our efforts to understand and target the fundamental mechanisms of autoimmune disease initiation and progression. Technologic innovations have recently accelerated our ability to discover key components of the processes leading to loss of tolerance and propagation of self-tissue damage in autoimmune conditions. The special issue "Cellular and Molecular Mechanisms of Autoimmunity" highlights many of these findings through primary research and review articles which detail advances in genetics, molecular processes, cellular functions, and host-pathogen interactions. Discussion of topics ranging from non-coding RNA and the complement cascade to T-cell aging and the microbiome uncovers exciting avenues for basic and clinical investigation. Importantly, the issue seeks to focus attention on both established and emerging mechanisms of autoimmunity to ultimately help improve the specificity, safety, and efficacy of treatments for this group of challenging immune disorders.

Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

Opioid Prescribing After Implementation of Single Click Access to a State Prescription Drug Monitoring Program Database in a Health System's Electronic Health Record.

OBJECTIVES: To determine the effect of one-click integration of a state's prescription drug monitoring program (PDMP) on the number of PDMP searches and opioid prescriptions, stratified by specialty. METHODS: Our large health system worked with the state department of public health to integrate the PDMP with the electronic health record (EHR), which enabled providers to query the data with a single click inside the EHR environment. We evaluated Schedule II or III opioid prescriptions reported to the Massachusetts PDMP 6 months before (November 15, 2017-May 15, 2018) and 6 months after (May 16, 2018, to November 16, 2018) integration. Search counts, prescriptions, patients, morphine milligram equivalents, as well as prescriber specialty were compared. RESULTS: There were 3,185 unique prescribers with a record of a Schedule II and/or III opioid prescription in both study periods that met inclusion criteria. After integration, the number of PDMP searches increased from 208,684 in the pre-integration phase to 298,478 searches in the post-integration phase (+43.0%). The number of opioid prescriptions dispensed decreased by 4.8%, the number of patients receiving a prescription decreased by 5.1%, and the mean morphine milligram equivalents (MMEs) per prescriber decreased by 5.4%. There were some notable specialty-specific differences in these measures. CONCLUSIONS: Integration of the PDMP into the EHR markedly increased the number of searches but was associated with modest decreases in opioids prescribed and patients receiving a prescription. Single click EHR integration of the PDMP, if implemented broadly, may be a way for states to significantly increase PDMP utilization.

Point-of-care cardiac ultrasound during cardiac arrest: a reliable tool for termination of resuscitation?

PURPOSE OF REVIEW: Point-of-care ultrasound (POCUS) is commonly used during cardiac arrest to screen for potential causes and to inform termination of resuscitation. However, unique biases and limitations in diagnostic and prognostic test accuracy studies lead to potential for misinterpretation. The present review highlights recent evidence regarding POCUS in cardiac arrest, guides the incorporation of POCUS into clinical management, and outlines how to improve the certainty of evidence. RECENT FINDINGS: Multiple frameworks organize and direct POCUS during cardiac arrest. Although many are proofs of concept, several have been prospectively evaluated. Indirect evidence from undifferentiated shock suggests that POCUS offers better specificity than sensitivity as a diagnostic aid. The prognostic accuracy of POCUS during cardiac arrest to predict subsequent clinical outcomes is better characterized, but subject to unique biases and confounding. Low certainty direct evidence suggests that POCUS offers better specificity than sensitivity as a prognostic aid. SUMMARY: POCUS findings might indicate a particular diagnosis or encourage the continuation of resuscitation, but absence of the same is not sufficient in isolation to exclude a particular diagnosis or cease resuscitation. Until the evidence to support POCUS during cardiac arrest is more certain, it is best characterized as a diagnostic and prognostic adjunct.

In†Situ Synthesis of an Aptamer-Based Polyvalent Antibody Mimic on the Cell Surface for Enhanced Interactions between Immune and Cancer Cells.

An ability to promote therapeutic immune cells to recognize cancer cells is important for the success of cell-based cancer immunotherapy. We present a synthetic method for functionalizing the surface of natural killer (NK) cells with a supramolecular aptamer-based polyvalent antibody mimic (PAM). The PAM is synthesized on the cell surface through nucleic acid assembly and hybridization. The data show that PAM has superiority over its monovalent counterpart in powering NKs to bind to cancer cells, and that PAM-engineered NK cells exhibit the capability of killing cancer cells more effectively. Notably, aptamers can, in principle, be discovered against any cell receptors; moreover, the aptamers can be replaced by any other ligands when developing a PAM. Thus, this work has successfully demonstrated a technology platform for promoting interactions between immune and cancer cells.

2018 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations Summary.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the second annual summary of International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations that includes the most recent cardiopulmonary resuscitation science reviewed by the International Liaison Committee on Resuscitation. This summary addresses the role of antiarrhythmic drugs in adults and children and includes the Advanced Life Support Task Force and Pediatric Task Force consensus statements, which summarize the most recent published evidence and an assessment of the quality of the evidence based on Grading of Recommendations, Assessment, Development, and Evaluation criteria. The statements include consensus treatment recommendations approved by members of the relevant task forces. Insights into the deliberations of each task force are provided in the Values and Preferences and Task Force Insights sections. Finally, the task force members have listed the top knowledge gaps for further research.

NF-kB signaling in myeloid cells mediates the pathogenesis of immune-mediated nephritis.

Immune-mediated glomerulonephritis is a serious end organ pathology that commonly affects patients with systemic lupus erythematosus (SLE). A classic murine model used to study lupus nephritis (LN) is nephrotoxic serum nephritis (NTN), in which mice are passively transferred nephrotoxic antibodies. We have previously shown that macrophages are important in the pathogenesis of LN. To further investigate the mechanism by which macrophages contribute to the pathogenic process, and to determine if this contribution is mediated by NF-κB signaling, we created B6 mice which had RelA knocked out in myeloid cells, thus inhibiting classical NF-κB signaling in this cell lineage. We induced NTN in this strain to assess the importance of macrophage derived NF-κB signaling in contributing to disease progression. Myeloid cell RelA knock out (KO) mice injected with nephrotoxic serum had significantly attenuated proteinuria, lower BUN levels, and improved renal histopathology compared to control injected wildtype B6 mice (WT). Inhibiting myeloid NF-κB signaling also decreased inflammatory modulators within the kidneys. We found significant decreases of IL-1a, IFNg, and IL-6 in kidneys from KO mice, but higher IL-10 expression. Flow cytometry revealed decreased numbers of kidney infiltrating classically activated macrophages in KO mice as well. Our results indicate that macrophage NF-κB signaling is instrumental in the contribution of this cell type to the pathogenesis of NTN. While approaches which decrease macrophage numbers can be effective in immune mediated nephritis, more targeted treatments directed at modulating macrophage signaling and/or function could be beneficial, at least in the early stages of disease.

The Association of the Average Epinephrine Dosing Interval and Survival With Favorable Neurologic Status at Hospital Discharge in Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: For patients with out-of-hospital cardiac arrest, the recommended dosing interval of epinephrine is 3 to 5 minutes, but this recommendation is based on expert opinion without data to guide optimal management. We seek to evaluate the association between the average epinephrine dosing interval and patient outcomes. METHODS: In a secondary analysis of the Resuscitation Outcomes Consortium continuous chest compression trial, we identified consecutive patients treated with greater than or equal to 2 doses of epinephrine. We defined average epinephrine dosing interval as resuscitation duration after the first dose of epinephrine divided by the total administered epinephrine, and categorized the dosing interval in minutes as less than 3, 3 to less than 4, 4 to less than 5, and greater than or equal to 5. We fit a logistic regression model to estimate the association of the average epinephrine dosing interval category with survival with favorable neurologic status (modified Rankin Scale score ≤3) at hospital discharge. RESULTS: We included 15,909 patients (median age 68 years [interquartile range 56 to 80 years], 35% women, 13% public location, 46% bystander cardiopulmonary resuscitation, and 19% initial shockable rhythm). The median epinephrine dosing interval was 4.3 minutes (interquartile range 3.5 to 5.3 minutes). Survival with favorable neurologic status occurred in 4.7% of patients. Compared with the reference dosing interval of less than 3 minutes, longer epinephrine dosing intervals were associated with lower survival with favorable neurologic status: dosing interval 3 to less than 4 minutes, adjusted odds ratio 0.44 (95% confidence interval 0.32 to 0.60); 4 to less than 5 minutes, adjusted odds ratio 0.26 (95% confidence interval 0.18 to 0.36); and greater than or equal to 5 minutes, adjusted odds ratio 0.21 (95% confidence interval 0.15 to 0.30). CONCLUSION: In this out-of-hospital cardiac arrest series, a shorter average epinephrine dosing interval was associated with improved survival with favorable neurologic status.

Long-Term Survival After Drowning-Related Cardiac Arrest.

BACKGROUND: Long-term outcomes after drowning-related cardiac arrest are not well characterized. OBJECTIVE: Our aims were to estimate long-term survival and identify prognostic factors in a large, population-based cohort of drowning victims with cardiac arrest. METHODS: We conducted a population-based prospective cohort study (1974-1996) of Western Washington Drowning Registry (WWDR) subjects with out-of-hospital cardiac arrest and attempted professional resuscitation. The primary outcome was long-term survival through 2012. We tabulated Utstein-style exposure variables, estimated Kaplan-Meier curves, and identified prognostic factors with Cox proportional hazard modeling. RESULTS: Of 2824 WWDR cases, 407 subjects (median age 17 years [interquartile range 3-33 years], 81% were male) were included. Only 54 (13%) were still alive after 1663 person-years of follow-up. Most deaths occurred after termination of initial resuscitation or during initial hospitalization. Risk of subsequent death after hospital discharge was 9.6 (95% confidence interval [CI] 5.7-15.9) per 1000 person-years. Long-term survival differed by Utstein variables (older age, illicit substance use, pre-drowning activity, submersion duration, cardiopulmonary resuscitation duration, intubation, defibrillation, and medications) and inpatient markers of illness severity (vital signs, Glasgow Coma Scale, laboratory values, shock). In adjusted analyses, older age (hazard ratio [HR] 1.01; 95% CI 1.01-1.02), epinephrine administration (HR 1.92; 95% CI 1.31-2.80), antiepileptic administration (HR 0.53; 95% CI 0.35-0.81), initial arterial pH (HR 0.49; 95% CI 0.26-0.92), and shock (HR 2.19; 95% CI 1.16-4.15) were associated with higher risk of death. CONCLUSIONS: Most cases of drowning-related cardiac arrest were fatal, but survivors to hospital discharge had a low risk of subsequent death that was independently associated with older age and clinical evidence of shock.

Emergency Physician-Initiated Resuscitative Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has several applications as a resuscitative intervention, including extracorporeal cardiopulmonary resuscitation (ECPR). ECPR is rarely initiated in the emergency department (ED) by emergency physicians outside regional academic institutions. OBJECTIVES: To evaluate whether ECPR improves clinical outcomes after cardiac arrest when initiated by emergency physicians (EPs) in a nonacademic hospital. METHODS AND MATERIALS: We performed a retrospective analysis of prospectively identified consecutive EP-initiated ECMO subjects from a single community hospital over a 7-year period. Logistic regression and propensity models tested the association between ECPR and survival to hospital discharge compared with concurrent ECPR-eligible control subjects. RESULTS: Over 7 years (2010-2017), EPs initiated ECMO on 58 subjects; 44 (76%) were venoarterial cases (43 ECPR) initiated in the ED. Of those, 11 (25%) survived to discharge (n = 9 with cerebral performance category score 1) and most were still alive after 5 years (66%). Adjusting for known covariates, ECPR subjects were more likely than concurrent controls to survive to discharge (odds ratio 8.4; 95% confidence interval 1.2-60.4). Propensity analysis revealed a favorable trend toward survival to discharge after ECPR (odds ratio 2.0; 95% confidence interval 0.51-7.8). CONCLUSIONS: Emergency physicians initiated ECMO with promising clinical outcomes. Prospective trials are needed to define the efficacy, safety, and cost-effectiveness of EP-initiated ECMO.

Does Non-Targeted Community CPR Training Increase Bystander CPR Frequency?

OBJECTIVE: Only 37% of out-of-hospital cardiac arrests (OHCA) receive bystander Cardiopulmonary resuscitation (CPR) in Kent County, MI. In May 2014, prehospital providers offered one-time, point-of-contact compression-only CPR training to 2,253 passersby at 7 public locations in Grand Rapids, Michigan. To assess the impact of this intervention, we compared bystander CPR frequency and clinical outcomes in regions surrounding training sites before and after the intervention, adjusting for prehospital covariates. We aimed to assess the effect of this broad, non-targeted intervention on bystander CPR frequency, type of CPR utilized, and clinical outcomes. We also tested for differences in geospatial variation of bystander CPR and clinical outcomes clustered around training sites. METHODS: Retrospective, observational, before-after study of adult, EMS-treated OHCA in Kent County from January 1, 2010 to December 31, 2015. We generated a 5-kilometer radius surrounding each training site to estimate any geospatial influence that training sites might have on bystander CPR frequency in nearby OHCA cases. Chi-squared, Fisher's exact, and t-tests assessed differences in subject features. Difference-in-differences analysis with generalized estimating equation (GEE) modeling assessed bystander CPR frequency, adjusting for training site, covariates (age, sex, witnessed, shockable rhythm, public location), and clustering around training sites. Similar modeling tested for changes in bystander CPR type, return of spontaneous circulation (ROSC), survival to hospital discharge, and cerebral performance category (CPC) of 1-2 at hospital discharge. RESULTS: We included 899 cases before and 587 cases post-intervention. Overall, we observed no increase in the frequency of bystander CPR or favorable clinical outcomes. We did observe an increase in compression-only CPR, but this was paradoxically restricted to OHCA cases falling outside radii around training sites. In adjusted modeling, the bystander CPR training intervention was not associated with bystander CPR frequency (ß -0.002; 95% CI -0.16, 0.15), compression-only CPR (ß -0.06; 95% CI -0.15, 0.02), ROSC (ß -0.06; 95% CI -0.21, 0.25), survival (ß -0.02; 95% CI -0.11, 0.06), or favorable neurologic outcome (ß -0.01; 95% CI -0.07, 0.09). CONCLUSIONS: We observed no impact in bystander CPR performance or outcomes from a blanket, non-targeted approach to community CPR education. The effect of targeted CPR education in locales with known low bystander CPR rates should be tested in this region.

Gains of Continuing Resuscitation in Refractory Out-of-hospital Cardiac Arrest: A Model-based Analysis to Identify Deaths Due to Intra-arrest Prognostication.

OBJECTIVE: Prognostication bias, in which a clinician predicts a negative outcome and terminates resuscitation (TR) thereby ensuring a poor outcome, is a rarely identified limitation of out-of-hospital cardiac arrest (OHCA) research. We sought to estimate the number of deaths due to intra-arrest prognostication in a cohort of OHCA's, and use this data to estimate the incremental benefit of continuing resuscitation. METHODS: This study examined a cohort of consecutive non-traumatic EMS-treated OHCAs from a provincial ambulance service, between 2007 and 2011 inclusive. We used Cox and logistic regression modeling, adjusting for Utstein covariates, to estimate the probability of ROSC, survival, and favorable neurological outcomes as a function of resuscitation time, and applied these models to estimate the number of missed survivors in those who had TR (prior to 20, 30, or 40 minutes). We determined the time juncture at which (1) the likelihood of survival fell below 1%, and (2) the proportion of survivors who had achieved ROSC exceeded 99%. RESULTS: Of 5674 adult EMS-treated cases, 46% achieved ROSC, and 12% survived. The median time of TR was 27.0 minutes (IQR 19.0-35.0). Continuing resuscitation until 40 minutes yielded an estimated 17 additional survivors (95% CI 13-21), 10 (95% CI 7-13) with favorable neurological outcomes. The probability of survival of those in refractory arrest decreased below 1% at 28 minutes (95% CI 24-30 minutes). At 36 minutes (95% CI 34-38 minutes) >99% of survivors had achieved ROSC. CONCLUSION: We identified possible deaths due to intra-arrest prognostication. Resuscitation should be continued for a minimum of 30 minutes in all patients, however for those with initial shockable rhythms 40 minutes appears to be warranted. Interventional trials and observational studies should standardize or adjust for duration of resuscitation prior to TR.

Development and validation of the Attitudes Towards Police Legitimacy Scale.

Although there is a substantial body of work examining attitudes towards the police, no measure has been developed to consistently capture citizens' beliefs regarding police legitimacy. Given that police conduct has garnered a great deal of attention, particularly in the last few years, the current research sought to develop a scale measuring perceptions of police legitimacy. Across multiple studies, items were created and the scale's factor structure explored (Study 1 and Study 2), the factor structure was confirmed (Study 3a), and the predictive validity of the scale was tested (Studies 3b-3d). Results provided evidence for a reliable and valid 34-item scale with a single-factor solution that predicted multiple outcomes, including justification of a police shooting (Study 3b) and resource allocation to a police charity (Study 3c), as well as correlations with self-reported criminal activity, right-wing authoritarianism, and social dominance orientation (Study 3d). We hope this scale will be useful in the study of police legitimacy, expanding the current literature, and improving police-community relations. (PsycINFO Database Record

Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest: Implications for Prolonging or Terminating Resuscitation.

BACKGROUND: Little evidence guides the appropriate duration of resuscitation in out-of-hospital cardiac arrest, and case features justifying longer or shorter durations are ill defined. We estimated the impact of resuscitation duration on the probability of favorable functional outcome in out-of-hospital cardiac arrest using a large, multicenter cohort. METHODS: This was a secondary analysis of a North American, single-blind, multicenter, cluster-randomized, clinical trial (ROC-PRIMED [Resuscitation Outcomes Consortium Prehospital Resuscitation Using an Impedance Valve and Early Versus Delayed]) of consecutive adults with nontraumatic, emergency medical services-treated out-of-hospital cardiac arrest. Primary exposure was duration of resuscitation in minutes (onset of professional resuscitation to return of spontaneous circulation [ROSC] or termination of resuscitation). Primary outcome was survival to hospital discharge with favorable outcome (modified Rankin scale [mRS] score of 0-3). Subjects were additionally classified as survival with unfavorable outcome (mRS score of 4-5), ROSC without survival (mRS score of 6), or without ROSC. Subject accrual was plotted as a function of resuscitation duration, and the dynamic probability of favorable outcome at discharge was estimated for the whole cohort and subgroups. Adjusted logistic regression models tested the association between resuscitation duration and survival with favorable outcome. RESULTS: The primary cohort included 11 368 subjects (median age, 69 years [interquartile range, 56-81 years]; 7121 men [62.6%]). Of these, 4023 (35.4%) achieved ROSC, 1232 (10.8%) survived to hospital discharge, and 905 (8.0%) had an mRS score of 0 to 3 at discharge. Distribution of cardiopulmonary resuscitation duration differed by outcome (P<0.00001). For cardiopulmonary resuscitation duration up to 37.0 minutes (95% confidence interval, 34.9-40.9 minutes), 99% with an eventual mRS score of 0 to 3 at discharge achieved ROSC. The dynamic probability of an mRS score of 0 to 3 at discharge declined over elapsed resuscitation duration, but subjects with initial shockable cardiac rhythm, witnessed cardiac arrest, and bystander cardiopulmonary resuscitation were more likely to survive with favorable outcome after prolonged efforts (30-40 minutes). After adjustment for prehospital (odds ratio, 0.93; 95% confidence interval, 0.92-0.95) and inpatient (odds ratio, 0.97; 95% confidence interval, 0.95-0.99) covariates, resuscitation duration was associated with survival to discharge with an mRS score of 0 to 3. CONCLUSIONS: Shorter resuscitation duration was associated with likelihood of favorable outcome at hospital discharge. Subjects with favorable case features were more likely to survive prolonged resuscitation up to 47 minutes. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00394706.