Introduction: Elevated intracranial pressure (ICP) is a devastating complication of brain injury, such as traumatic brain injury, subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, and other conditions. Delay to diagnosis and treatment are associated with increased morbidity and mortality. For Emergency Department (ED) physicians, invasive ICP measurement is typically not available. We sought to summarize and compare the accuracy of physical examination, imaging, and ultrasonography of the optic nerve sheath diameter (ONSD) for diagnosis of elevated ICP. Methods: We searched Medline, EMBASE and 4 other databases from inception through August 2018. We included only English studies (randomized controlled trials, cohort and case-control studies). Gold standard was ICP≥20 mmHg on invasive ICP monitoring. Two reviewers independently screened studies and extracted data. We assessed risk of bias using Quality Assessment of Diagnostic Accuracy Studies 2 criteria. Hierarchical Summary Receiver Operating Characteristic model generated summary diagnostic accuracy estimates. Results: We included 37 studies (n = 4,768, kappa = 0.96). Of exam signs, pooled sensitivity and specificity for increased ICP were: mydriasis (28.2% [95% CI: 16.0-44.8], 85.9.0% [95% CI: 74.9-92.5]), motor posturing (54.3% [95% CI: 36.6-71.0], 63.6% [95% CI: 46.5-77.8]) and Glasgow Coma Scale (GCS) ≤8 (75.8% [95% CI: 62.4-85.5], 39.9% [95% CI: 26.9-54.5]). Computed tomography findings: compression of basal cisterns had 85.9% [95% CI: 58.0-96.4] sensitivity and 61.0% [95% CI: 29.1-85.6] specificity; any midline shift had 80.9% [95% CI: 64.3-90.9] sensitivity and 42.7% [95% CI: 24.0-63.7] specificity; midline shift≥1cm had 20.7% [95% CI: 13.0-31.3] sensitivity and 89.2% {95% CI: 77.5-95.2] specificity. Finally, pooled area under the ROC curve describing accuracy for ONSD sonography for ICP was 0.94 (95% CI: 0.91-0.96). Conclusion: The absence of any one physical exam feature (e.g. mydriasis, posturing, or decreased GCS) is not sufficient to rule-out elevated ICP. Significant midline shift is highly suggestive of elevated ICP, but absence of shift does not rule it out. ONSD sonography may be useful in diagnosing elevated ICP. High suspicion of elevated ICP may necessitate treatment and transfer to a centre capable of invasive ICP monitoring.

Introduction: We wished to identify emergency department interventions that lead to improvement in door-to-ECG times for adults presenting with symptoms suggestive of acute coronary syndrome (ACS). Methods: Two reviewers searched Medline, Embase, CINAHL and Cochrane CENTRAL from inception to April 2018 for studies in adult emergency departments with an identifiable intervention to reduce median door-to-ECG times when compared to the institution's baseline. Quality was assessed using the ‘Quality Improvement Minimum Quality Criteria Set’ (QI-MQCS) critical appraisal tool. The primary outcome was the absolute median reduction in door-to-ECG times as calculated by the difference between the post-intervention time and pre-intervention time. Results: Two reviewers identified 809 unique articles, yielding 11 before-after quality improvement studies that met eligibility criteria (N = 15,622 patients). The majority of studies (10/11) reported bundled interventions and most (10/11) showed statistical improvement in door-to-ECG times. The most common interventions were: having a dedicated ECG machine and technician in triage (5/11); improved triage education (4/11); improved triage disposition (2/11); and data feedback mechanisms (1/11). Conclusion: There are multiple interventions that show promise for reducing emergency department door-to-ECG times. Effective bundled interventions include having a dedicated ECG technician, triage education and better triage disposition. These changes, bundled together, can help intuitions attain best practice guidelines. Emergency departments must first understand their local context before adopting any single or group of interventions.

Introduction: Risk-stratification of patients requiring endotracheal intubation and mechanical ventilation in the Emergency Department (ED) is necessary for informed discussions with patients regarding goals-of-care. Frailty is a clinical state characterized by reduced physiologic reserve, and resulting from accumulation of physiological stresses and comorbid disease. Frailty is increasingly being identified as an important independent predictor of outcome among critically ill patients. Our objective was to identify the impact of clinical frailty (defined by the Clinical Frailty Scale [CFS]) on in-hospital mortality and resource utilization of ED patients requiring endotracheal intubation and mechanical ventilation. Methods: We analyzed a prospectively collected registry (2011-2016) of patients requiring endotracheal intubation in the ED at two academic hospitals and six community hospitals. We included all patients ≥18 years of age, who survived to the point of ICU admission. All patient information, outcomes, and resource utilization were stored in the registry. CFS scores were obtained through chart abstraction by two blinded reviewers. The primary outcome, in-hospital mortality, was analyzed using a multivariable logistic regression model, controlling for confounding variables (including patient sex, comorbidities, and illness severity). We defined “frailty” as a CFS ≥ 5. Results: 4,622 patients were included. Mean age was 61.2 years (SD: 17.5), and 2,614 (56.6%) were male. Frailty was associated with increased risk of in-hospital mortality, as compared to those who were not frail (adjusted odds ratio [OR] 2.21 [1.98-2.51]). Frailty was also associated with higher likelihood of discharge to long-term care (adjusted OR 1.78 [1.56-2.01]) among patients initially from a home setting. Frail patients were more likely to fail extubation during their hospitalization (adjusted OR 1.81 [1.67-1.95]) and were more likely to require tracheostomy (adjusted OR 1.41 [1.34-1.49]). Conclusion: Presence of frailty among ED patients requiring endotracheal intubation and mechanical ventilation was associated with increased in-hospital mortality, discharge to long-term care, extubation failure, and tracheostomy. ED physicians should consider the impact of frailty on patient outcomes, and discuss associated prognosis with patients prior to intubation.

Introduction: For rhythm control of acute atrial fibrillation (AAF) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAF, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an apriori-specified modified intention-to-treat (MITT) basis excluding patients who never received the study infusion (e.g. spontaneous conversion). Data were analyzed using chi-squared tests and logistic regression. Our target sample size was 374 evaluable patients. Results: Of 395 randomized patients, 18 were excluded from the MITT analysis; none were lost to follow-up. The Drug-Shock (N = 198) and Shock Only (N = 180) groups (total = 378) were similar for all characteristics including mean age (60.0 vs 59.5 yrs), duration of AAF (10.1 vs 10.8 hrs), previous AF (67.2% vs 68.3%), median CHADS2 score (0 vs 0), and mean initial heart rate (119.9 vs 118.0 bpm). More patients converted to normal sinus rhythm in the Drug-Shock group (97.0% vs 92.2%; absolute difference 4.8%, 95% CI 0.2-9.9; P = 0.04). The multivariable analyses confirmed the Drug-Shock strategy superiority (P = 0.04). There were no statistically significant differences for time to conversion (91.4 vs 85.4 minutes), total ED length of stay (7.1 vs 7.7 hours), disposition home (97.0% vs 96.1%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion was more common in the Drug-Shock group (8.1% vs 0.6%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAF patients to go home in sinus rhythm. A strategy of initial cardioversion with procainamide was superior to a strategy of immediate ECV.

Civil suits for damage awards against police officers alleged to have engaged in illegal searches have long been suggested as an alternative to the exclusionary rule as a remedy for police misconduct. A review of empirical literature on the incidence and outcomes of such suits suggests that defendant officers often prevail and that the awards do not seem large enough to produce the punishment and deterrence effect often claimed by proponents of the tort remedy. Using an experimental technique involving simulated trials and adults called for jury service as subjects, we examine the effects of two procedural aspects of such suits on juror awards. The extent of municipal liability and the substitution of the U.S. government as plaintiff do not appear to affect the incidence or size of compensatory or punitive damage awards. Denying jurors information about the outcome of the search does appear likely to increase damage awards. The article both explores factors affecting juror decision-making in these cases and illustrates the utility and limitations of the experimental method for testing suggested policy innovations.

Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to innate and adaptive immune response defects in cancers that allow virus replication, and the requirement for cell division for virus integration into the genome. Toca 511 spreads through tumors, stably delivering an optimized yeast cytosine deaminase gene that converts the prodrug Toca FC (investigational, extended-release 5-FC) into 5-FU within the tumor microenvironment. 5-FU kills infected dividing cancer cells and surrounding tumor, myeloid derived suppressor cells, and tumor associated macrophages, resulting in long-term tumor immunity in preclinical models. Data from a Phase 1 resection trial showed six durable CRs and extended mOS compared to historical controls. The FDA granted Breakthrough Therapy Designation for Toca 511 & Toca FC in the treatment of patients with rHGG. Toca 5 is an international, randomized, open-label Phase 3 trial (NCT02414165) of Toca 511 & Toca FC versus SOC in patients undergoing resection for first or second recurrence of rHGG. Patients will be stratified by IDH1 status, KPS, and geographic region. Primary endpoint is OS, and secondary endpoints are durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. Key inclusion criteria are histologically proven GBM or AA, tumor size ≥1cm and ≤5cm, and KPS ≥70. Immune monitoring and molecular profiling will be performed. Approximately 380 patients will be randomized. An IDMC is commissioned to review the safety and efficacy data which includes 2 interim analyses. Enrollment is ongoing.

Identifying optimal out-of-home placements for child welfare-involved youth is challenging. Examples of youth recovering within each “out-of-home” placement type (foster, relative, residential) are evident, as are examples of youth who are deteriorating. The heterogeneity in developmental history and current functioning of youth makes blanket policies regarding placement unwise. Examination of developmental heterogeneity and functioning of youth in the welfare system can provide insights about factors influencing outcomes, thereby informing practice, program and policy. We explore whether current relational health (connectedness) promotes positive outcomes for child welfare-involved youth while controlling for developmental risk (history of adverse, and lack of relationally positive, experiences). Clinicians at 19 organisations serving child welfare-involved youth used a neurodevelopmentally informed approach to intervention, the Neurosequential Model of Therapeutics (NMT), which includes metrics to assess the developmental timing of children's risk, “connectedness” and neurodevelopmental functioning (e.g., sleep, arousal, cortical control). Data-driven statistical techniques were used to produce stable, generalisable estimates. Risk during the perinatal (0–2 months) period significantly predicted children's functioning; current relational health predicted outcomes more strongly. Although early life developmental risk has a persistent effect on functioning, relationally supportive contexts may mitigate this risk. Improving relational contexts of child welfare-involved youth, regardless of placement type, is key.

Introduction: Sepsis remains a major cause of mortality. In the Emergency Department (ED), rapid identification and management of sepsis have been associated with improved outcomes. Following ED assessment, patients with infection may be directly admitted to the Intensive Care Unit (ICU), or alternatively admitted to hospital wards or sent home, with risk of future deterioration necessitating ICU admission. Little is known regarding outcomes and costs of ICU sepsis patients who are initially admitted to a ward or discharged home (delayed ICU admission), as compared to those with direct ICU admission from the ED. Methods: We analyzed a prospectively collected registry (2011-2014) of patients admitted to the ICU with a diagnosis of sepsis at two academic hospitals. We included all adult patients with an index ED visit within 72 hours of ICU admission. Patients were categorized into 3 groups: 1) Admitted directly to ICU; 2) Admitted to wards, with ICU admission within 72 hours; and 3) Sent home, with ICU admission within 72 hours. ICU length of stay (LOS) and total costs (both direct and indirect) were recorded. The primary outcome, in-hospital mortality, was analyzed using a multivariable logistic regression model, controlling for confounding variables (including patient sex, comorbidities, and illness severity). Results: 657 ICU patients were included. Of these, 338 (51.4%) were admitted directly from ED to ICU, 246 (37.4%) were initially admitted to the wards, and 73 (11.1%) were initially sent home. In-hospital mortality was lowest amongst patients admitted directly to the ICU (29.5%), as compared to patients admitted to ICU from wards (42.7%), or home (61.6%). Delayed ICU admission was associated with increased odds of mortality (adjusted odds ratio 1.85 [1.24-2.76], P<0.01) and increased median ICU LOS (11 days vs. 4 days, P<0.001). Median total costs were lowest among patients directly admitted to the ICU ($19,924, [Interquartile range [IQR], 10,333-32,387]), as compared to those admitted from wards ($72,155 [IQR, $42,771-122,749]) and those initially sent home ($45,121 [IQR, $19,930-86,843]). Conclusion: Only half of ED sepsis patients ultimately requiring ICU admission within 72 hours of ED arrival are directly admitted to the ICU. Delayed ICU admission is associated with higher mortality, LOS, and costs.

Following a cluster of serious pseudomonas skin infections linked to a body piercing and tattooing premises, a look-back exercise was carried out to offer clients a screen for blood-borne viruses. Of those attending for screening 72% (581/809) had a piercing procedure in the premises of interest: 94 (16%) were under 16 years of age at the time of screening. The most common site of piercing was ear (34%), followed by nose (27%), nipple (21%) and navel (21%). A small number (<5) tested positive for hepatitis B and C, with no evidence this was linked to the premises. However, 36% (211/581) of clients reported a skin infection associated with their piercing. Using data from client forms, 36% provided a false age. Those aged under 16 years (OR 4.5, 95% CI 2.7–7.7) and those receiving a piercing at an intimate site (OR 2.1, 95% CI 1.3–3.6) were more likely to provide a false age. The findings from this exercise were used to support the drafting of the Public Health (Wales) Bill which proposed better regulation of piercing premises and the need to provide proof of being 18 years of age or over before having a piercing of an intimate site.

This paper discusses the sustainability of livestock systems, emphasising bidirectional relations with animal health. We review conventional and contrarian thinking on sustainability and argue that in the most common approaches to understanding sustainability, health aspects have been under-examined. Literature review reveals deep concerns over the sustainability of livestock systems; we recognise that interventions are required to shift to more sustainable trajectories, and explore approaches to prioritising in different systems, focusing on interventions that lead to better health. A previously proposed three-tiered categorisation of ‘hot spots’, ‘cold spots’ and ‘worried well’ animal health trajectories provides a mental model that, by taking into consideration the different animal health status, animal health risks, service response needs and key drivers in each system, can help identify and implement interventions. Combining sustainability concepts with animal health trajectories allows for a richer analysis, and we apply this to three case studies drawn from North Africa and the Middle East; Bangladesh; and the Eastern Cape of South Africa. We conclude that the quest for sustainability of livestock production systems from the perspective of human and animal health is elusive and difficult to reconcile with the massive anticipated growth in demand for livestock products, mainly in low- and middle-income countries, as well as the aspirations of poor livestock keepers for better lives. Nevertheless, improving the health of livestock can contribute to health sustainability both through reducing negative health impacts of livestock and increasing efficiency of production. However, the choice of the most appropriate options must be under-pinned by an understanding of agro-ecology, economy and values. We argue that a new pillar of One Health should be added to the three traditional sustainability pillars of economics, society and environment when addressing livestock systems.

Children reared in impoverished environments are at risk for enduring psychological and physical health problems. Mechanisms by which poverty affects development, however, remain unclear. To explore one potential mechanism of poverty's impact on social–emotional and cognitive development, an experimental examination of a rodent model of scarcity-adversity was conducted and compared to results from a longitudinal study of human infants and families followed from birth (N = 1,292) who faced high levels of poverty-related scarcity-adversity. Cross-species results supported the hypothesis that altered caregiving is one pathway by which poverty adversely impacts development. Rodent mothers assigned to the scarcity-adversity condition exhibited decreased sensitive parenting and increased negative parenting relative to mothers assigned to the control condition. Furthermore, scarcity-adversity reared pups exhibited decreased developmental competence as indicated by disrupted nipple attachment, distress vocalization when in physical contact with an anesthetized mother, and reduced preference for maternal odor with corresponding changes in brain activation. Human results indicated that scarcity-adversity was inversely correlated with sensitive parenting and positively correlated with negative parenting, and that parenting fully mediated the association of poverty-related risk with infant indicators of developmental competence. Findings are discussed from the perspective of the usefulness of bidirectional–translational research to inform interventions for at-risk families.

Current commercial poultry production in the UK faces many challenges which make it difficult to confidently predict the future. Changing legislation, responding largely to welfare pressures, is one such challenge. Additionally, consumer demands are widening. Eggs and meat from stock which is organically produced, or fed on rations containing no genetically modified ingredients, or free range produced, or corn fed are some of the assurances sought by the purchaser and consumer. Although the market place already offers such produce it is difficult to predict the extent to which they will penetrate a market which developed largely through the use of intensive production systems. The alternatives to intensively produced eggs and meat are more expensive to produce and therefore purchase and consequently are susceptible to changes in standards of living and the affluence of the consumer.

This paper briefly describes current commercial practices and some of the specific challenges arising from new legislation.

A description of some specific requirements of birds highlights areas where improvements, in terms of performance, production efficiency, and welfare might be gained. Since the overwhelming majority of eggs and meat is produced in intensive, highly automated systems, there is an obvious need for an integrated approach featuring engineers and the poultry industry to refine and further develop technology which better serves the birds, and ultimately, the consumer.

It is concluded that the UK cannot compete in production costs with some other areas of the world and as retailers increasingly source their goods worldwide, the UK poultry producer may have to resort to the production of products which satisfy niche demands.

In determining research priorities, as well as in evaluating the relative merits of different disease control options, there is an increasing demand for impact assessment, in order to justify and support research and development investments. In this process, quantitative epidemiology has a significant role to play. This paper first outlines the categories of impacts that diseases have on society and discusses how these can be measured. Using the example of tick-borne infections of livestock, the paper describes five quantitative epidemiological tools that can be used in impact assessment. These are: geographical information systems (GIS) to estimate disease distribution; mathematical models to quantify infection dynamics; observational field studies to link infection status with production loss; statistical models to enhance study design; and spreadsheet models for economic impact assessment. In each category, examples are given of recent studies.

We examined associations between specific self-regulatory mechanisms and externalizing behavior patterns from ages 2 to 15 (N = 443). The relation between multiple self-regulatory indicators across multiple domains (i.e., physiological, attentional, emotional, and behavioral) at age 2 and at age 5 and group membership in four distinct externalizing trajectories was examined. By examining each of these self-regulatory processes in combination with one another, and therefore accounting for their shared variance, we aimed to better understand which specific self-regulatory skills were associated most strongly with externalizing behavioral patterns. Findings suggest that behavioral inhibitory control and emotion regulation are particularly important in distinguishing between children who show normative declines in externalizing behaviors across early childhood and those who demonstrate high levels through adolescence.

Enlist™ cotton contains the aad-12 and pat genes that confer resistance to 2,4-D and glufosinate, respectively. Thirty-three field trials were conducted focused on Enlist cotton injury from glufosinate as affected by cotton growth stage, application rate, and single or sequential applications. Maximum injury from a single application of typical 1X (542 g ae ha-1) and 2X use rates was 3 and 13%, respectively, regardless of growth stage. Injury from sequential applications of 1X or 2X rates was equivalent to single applications. Similar injury was observed with four commercial formulations of glufosinate. Cotton yield was never affected by glufosinate. This research demonstrates Enlist™ cotton has robust resistance to glufosinate at rates at least twice the typical use rate when applied once or twice at growth stages ranging from 2 to 12 leaves.