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Introduction: Patients hospitalized following a trauma will be frequently treated with opioids during their stay and after discharge. We examined the relationship between acute phase (< 3 months) opioid use after discharge and the risk of opioid poisoning (OP) or opioid use disorder (OUD) in older trauma patients Methods: In a retrospective multicenter cohort study conducted on registry data, we included all patients aged 65 years and older admitted (hospital stay >2 days) for injury in 57 trauma centers in the province of Quebec (Canada) between 2004 and 2014. We searched for OP and OUD from ICD-9 and ICD-10 code diagnosis that resulted in a hospitalization or a medical consultation after their initial injury. Patients that filled an opioid prescription within a 3-month period after sustaining the trauma were compared to those who did not fill an opioid prescription during that period using Cox proportional hazards regressions. Results: A total of 70,314 participants were retained for analysis; median age was 82 years (IQR: 75-87), 68% were women, and 34% of the patients filled an opioid prescription within 3-months of the initial trauma. During a median follow-up of 2.6 years (IQR: 1-5), 192 participants (0.30%; 95%CI: 0.25%-0.35%) were hospitalized for OP and 73 (0.10%; 95%CI: 0.07%-0.13%) were diagnosed with OUD. Having filled an opioid prescription within 3-months of injury was associated with an increased hazard ratio of OP (2.6; 95%CI: 1.9-3.5) and OUD (4.0; 95%CI: 2.3-7.0). However, history of OP (2.7; 95%CI: 1.2-6.1), of substance use disorder (4.3; 95%CI: 2.4-7.9), or of opioid prescription filled (2.7; 95%CI: 2.1-3.5) before trauma were also related to OP or OUD. Conclusion: Opioid poisoning and opioid use disorder are rare events after hospitalization for trauma in older patients. However, opioids should be used cautiously in patients with history of substance use disorder, opioid poisoning or opioid use during the past year.
The Dietary Approaches to Stop Hypertension (DASH) eating pattern has been shown to reduce blood pressure (BP) in previous clinical trials. In the PREMIER study, an established behavioural intervention, with or without DASH, promoted greater weight loss than an advice-only control group, but effects of the DASH intervention on BP were weaker. In these analyses, PREMIER data were used to evaluate whether change in dairy product or fruit and vegetable (FV) intake during the first six intervention months impacted changes in weight and/or BP. Study participants were classified as having low or high intakes of dairy products (<1·5 v. ≥1·5 servings/d) and FV (<5 v. ≥5 servings/d) at baseline and 6 months. For dairy products, in particular, participants with higher baseline intakes tended to decrease their intakes during the intervention. In these analyses, subjects consuming <1·5 dairy servings/d at baseline whose intake increased during the intervention lost more weight than those whose intake decreased or remained low throughout (10·6 v. 7·0 pounds (4·8 v. 3·2 kg) lost, respectively, P = 0·002). The same was true for FV intake (11·0 v. 5·9 pounds (5·0 v. 2·7 kg) lost, P < 0·001). We also found synergistic effects of dairy products and FV on weight loss and BP reduction. Specifically, subjects who increased their intakes of dairy products and also consumed ≥5 servings of FV/d lost more weight and had greater reductions in BP than other groups; in addition, higher FV intakes had the greatest benefit to BP among those consuming more dairy products. These results provide evidence that the DASH pattern was most beneficial to individuals whose baseline diet was less consistent with DASH.
Nearly half of care home residents with advanced dementia have clinically significant agitation. Little is known about costs associated with these symptoms toward the end of life. We calculated monetary costs associated with agitation from UK National Health Service, personal social services, and societal perspectives.
Prospective cohort study.
Thirteen nursing homes in London and the southeast of England.
Seventy-nine people with advanced dementia (Functional Assessment Staging Tool grade 6e and above) residing in nursing homes, and thirty-five of their informal carers.
Data collected at study entry and monthly for up to 9 months, extrapolated for expression per annum. Agitation was assessed using the Cohen-Mansfield Agitation Inventory (CMAI). Health and social care costs of residing in care homes, and costs of contacts with health and social care services were calculated from national unit costs; for a societal perspective, costs of providing informal care were estimated using the resource utilization in dementia (RUD)-Lite scale.
After adjustment, health and social care costs, and costs of providing informal care varied significantly by level of agitation as death approached, from £23,000 over a 1-year period with no agitation symptoms (CMAI agitation score 0–10) to £45,000 at the most severe level (CMAI agitation score >100). On average, agitation accounted for 30% of health and social care costs. Informal care costs were substantial, constituting 29% of total costs.
With the increasing prevalence of dementia, costs of care will impact on healthcare and social services systems, as well as informal carers. Agitation is a key driver of these costs in people with advanced dementia presenting complex challenges for symptom management, service planners, and providers.
Recent comparisons between classical Wagner theory for the impact of two liquid droplets and direct numerical simulations in Cimpeanu & Moore (J. Fluid Mech., vol. 856, 2018, pp. 764–796) show that, in some regimes, the inviscid theory over-predicts the thickness of the root of the splash jet that forms in the impact, while also struggling to predict the angle at which the jet is emitted. The effect of capillary and viscous perturbations to Helmholtz flows was investigated in a previous study, see Moore et al. (J. Fluid Mech., vol. 742, 2014, R1). However, the paper in question ignored a term in the second-order perturbation analysis, which needs to be included in order to predict the displacement of the inviscid free boundary to lowest order. In this paper, we derive a singular integro-differential equation for the free-surface perturbations caused by viscosity in Helmholtz flows and discuss its application both in the context of Wagner theory and more generally. In particular, viscosity can induce non-monotonic behaviour in the free boundary profiles near points of maximum curvature.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
This study evaluated the efficacy of a family-centered preventive intervention, the Family Check-Up (FCU), delivered as an online, eHealth model to middle school families. To increase accessibility of family-centered prevention in schools, we adapted the evidence-based FCU to an online format, with the goal of providing a model of service delivery that is feasible, given limited staffing and resources in many schools. Building on prior research, we randomly assigned participants to waitlist control (n = 105), FCU Online as a web-based intervention (n = 109), and FCU Online with coaching support (n = 108). We tested the effects of the intervention on multiple outcomes, including parental self-efficacy, child self-regulation, and child behavior, in this registered clinical trial (NCT03060291). Families engaged in the intervention at a high rate (72% completed the FCU assessment) and completed 3-month posttest assessments with good retention (94% retained). Random assignment to the FCU Online with coaching support was associated with reduced emotional problems for children (p = .003, d = −0.32) and improved parental confidence and self-efficacy (p = .018, d = 0.25) when compared with waitlist controls. Risk moderated effects: at-risk youth showed stronger effects than did those with minimal risk. The results have implications for online delivery of family-centered interventions in schools.
The Wisconsin Twin Project comprises multiple longitudinal studies that span infancy to early adulthood. We summarize recent papers that show how twin designs with deep phenotyping, including biological measures, can inform questions about phenotypic structure, etiology, comorbidity, heterogeneity, and gene–environment interplay of temperamental constructs and mental and physical health conditions of children and adolescents. The general framework for investigations begins with rich characterization of early temperament and follows with study of experiences and exposures across childhood and adolescence. Many studies incorporate neuroimaging and hormone assays.
We read with interest the recent editorial, “The Hennepin Ketamine Study,” by Dr. Samuel Stratton commenting on the research ethics, methodology, and the current public controversy surrounding this study.1 As researchers and investigators of this study, we strongly agree that prospective clinical research in the prehospital environment is necessary to advance the science of Emergency Medical Services (EMS) and emergency medicine. We also agree that accomplishing this is challenging as the prehospital environment often encounters patient populations who cannot provide meaningful informed consent due to their emergent conditions. To ensure that fellow emergency medicine researchers understand the facts of our work so they may plan future studies, and to address some of the questions and concerns in Dr. Stratton’s editorial, the lay press, and in social media,2 we would like to call attention to some inaccuracies in Dr. Stratton’s editorial, and to the lay media stories on which it appears to be based.
Ho JD, Cole JB, Klein LR, Olives TD, Driver BE, Moore JC, Nystrom PC, Arens AM, Simpson NS, Hick JL, Chavez RA, Lynch WL, Miner JR. The Hennepin Ketamine Study investigators’ reply. Prehosp Disaster Med. 2019;34(2):111–113
Adverse childhood experiences (ACEs) have an impact on women's adaptation to parenthood, but mechanisms are poorly understood. Autonomic nervous system reactivity was tested as a potential mediating mechanism in a sample of 193 at-risk primiparous women. ACEs were measured retrospectively during pregnancy. A baby cry-response task was administered during pregnancy while indicators of sympathetic reactivity (pre-ejection period; PEP) and parasympathetic reactivity (respiratory sinus arrhythmia; RSA) were recorded. Parenting self-efficacy, anxiety, and depressive symptoms were measured during pregnancy and 1 year after giving birth. Harsh discipline was measured 2 years after giving birth. Structural equation modeling was employed to test whether baseline PEP and RSA and reactivity mediated links between ACEs and postnatal outcomes, adjusted for prenatal variables. High ACEs predicted less RSA reactivity (p = .02), which subsequently predicted increases in depressive symptoms (p = .03). The indirect effect was not significant (p = .06). There was no indirect link between high ACEs and harsh parenting through PEP nor RSA (n = 98). The parasympathetic nervous system may be involved in negative affective responses in the transition to parenthood among women exposed to childhood trauma.
Objectives: Caregivers of youth with heavy prenatal alcohol exposure report impaired communication, which can significantly impact quality of life. Using data collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), we examined whether cognitive variables predict communication ability of youth with histories of heavy prenatal alcohol exposure. Methods: Subjects (ages 10–16 years) comprised two groups: adolescents with heavy prenatal alcohol exposure (AE) and non-exposed controls (CON). Selected measures of executive function (NEPSY, Delis-Kaplan Executive Function System), working memory (CANTAB), and language were tested in the child, while parents completed communication ratings (Vineland Adaptive Behavior Scales – Second Edition). Separate multiple regression analyses determined which cognitive domains predicted communication ability. A final, global model of communication comprised the three cognitive models. Results: Spatial Working Memory and Inhibition significantly contributed to communication ability across groups. Twenty Questions performance related to communication ability in the CON group only while Word Generation performance related to communication ability in the AE group only. Effects remained significant in the global model, with the exception of Spatial Working Memory. Conclusions: Both groups displayed a relation between communication and Spatial Working Memory and Inhibition. Stronger communication ability related to stronger verbal fluency in the AE group and Twenty Questions performance in the CON group. These findings suggest that alcohol-exposed adolescents may rely more heavily on learned verbal storage or fluency for daily communication while non-exposed adolescents may rely more heavily on abstract thinking and verbal efficiency. Interventions aimed at aspects of executive function may be most effective at improving communication ability of these individuals. (JINS, 2018, 24, 1026–1037)
We perform a thorough qualitative and quantitative comparison of theoretical predictions and direct numerical simulations for the two-dimensional, vertical impact of two droplets of the same fluid. In particular, we show that the theoretical predictions for the location and velocity of the jet root are excellent in the early stages of the impact, while the predicted jet velocity and thickness profiles are also in good agreement with the computations before the jet begins to bend. By neglecting the role of the surrounding gas both before and after impact, we are able to use Wagner theory to describe the early-time structure of the impact. We derive the model for general droplet velocities and radii, which encompasses a wide range of impact scenarios from the symmetric impact of identical drops to liquid drops impacting a deep pool. The leading-order solution is sufficient to predict the curve along which the root of the high-speed jet travels. After moving into a frame fixed in this curve, we are able to derive the zero-gravity shallow-water equations governing the leading-order thickness and velocity of the jet. Our numerical simulations are performed in the open-source software Gerris, which allows for the level of local grid refinement necessary for a problem with such a wide variety of length scales. The numerical simulations incorporate more of the physics of the problem, in particular the surrounding gas, the fluid viscosities, gravity and surface tension. We compare the computed and predicted solutions for a range of droplet radii and velocities, finding excellent agreement in the early stage. In light of these successful comparisons, we discuss the tangible benefits of using Wagner theory to confidently track properties such as the jet-root location, jet thickness and jet velocity in future studies of splash jet/ejecta evolution.
A hierarchy of models is formulated for the deflection of a thin two-dimensional liquid jet as it passes over a thin air-cushioning layer above a rigid flat impermeable substrate. We perform a systematic derivation of the leading-order equations of motion for the jet in the distinguished limit in which the air pressure jump, surface tension and gravity affect the displacement of the centreline of the jet, but not its thickness or velocity. We identify thereby the axial length scales for centreline deflection in regimes in which the air layer is dominated by viscous or inertial effects. The derived length scales and reduced equations aim to expand the suite of tools available for future analyses of the evolution of lamellae and ejecta in impact problems. Assuming that the jet is sufficiently long that tip and entry effects can be neglected, we demonstrate that the centreline of a constant-thickness jet moving with constant axial speed is destabilised by the air layer for sufficiently small surface tension. Expressions for the fastest-growing modes are obtained in both the viscous-dominated air and inertia-dominated air regimes. For a finite-length jet emanating from a nozzle, we show that, in one particular asymptotic limit, the evolution of the jet centreline is akin to the flapping of an unfurling flag above a thin air layer. We discuss the distinguished limit in which tip retraction can be neglected and perform numerical investigations into the resulting model. We show that the cushioning layer causes the jet centreline to bend, leading to rupture of the air layer. We discuss how our toolbox of models can be adapted and utilised in the context of recent experimental and numerical studies of splash dynamics.
The genetic and environmental contributions of negative valence systems (NVS) to internalizing pathways study (also referred to as the Adolescent and Young Adult Twin Study) was designed to examine varying constructs of the NVS as they relate to the development of internalizing disorders from a genetically informed perspective. The goal of this study was to evaluate genetic and environmental contributions to potential psychiatric endophenotypes that contribute to internalizing psychopathology by studying adolescent and young adult twins longitudinally over a 2-year period. This report details the sample characteristics, study design, and methodology of this study. The first wave of data collection (i.e., time 1) is complete; the 2-year follow-up (i.e., time 2) is currently underway. A total of 430 twin pairs (N = 860 individual twins; 166 monozygotic pairs; 57.2% female) and 422 parents or legal guardians participated at time 1. Twin participants completed self-report surveys and participated in experimental paradigms to assess processes within the NVS. Additionally, parents completed surveys to report on themselves and their twin children. Findings from this study will help clarify the genetic and environmental influences of the NVS and their association with internalizing risk. The goal of this line of research is to develop methods for early internalizing disorder risk detection.
Neospora caninum is a coccidian intracellular protozoan capable of infecting a wide range of mammals, although severe disease is mostly reported in dogs and cattle. Innate defences triggered by monocytes/macrophages are key in the pathogenesis of neosporosis, as these cells are first-line defenders against intracellular infections. The aim of this study was to characterize infection and innate responses in macrophages infected with N. caninum using a well-known cell model to study macrophage functions (human monocyte THP-1 cells). Intracellular invasion of live tachyzoites occurred as fast as 4 h (confirmed with immunofluorescence microscopy using N. caninum-specific antibodies). Macrophages infected by N. caninum had increased expression of pro-inflammatory cytokines (TNFα, IL-1β, IL-8, IFNγ). Interestingly, N. caninum induced expression of host-defence peptides (cathelicidins), a mechanism of defence never reported for N. caninum infection in macrophages. The expression of cytokines and cathelicidins in macrophages invaded by N. caninum was mediated by mitogen-activated protein kinase (MEK 1/2). Secretion of such innate factors from N. caninum-infected macrophages reduced parasite internalization and promoted the secretion of pro-inflammatory cytokines in naïve macrophages. We concluded that rapid invasion of macrophages by N. caninum triggered protective innate defence mechanisms against intracellular pathogens.
Animal models of early postnatal mother–infant interactions have highlighted the importance of tactile contact for biobehavioral outcomes via the modification of DNA methylation (DNAm). The role of normative variation in contact in early human development has yet to be explored. In an effort to translate the animal work on tactile contact to humans, we applied a naturalistic daily diary strategy to assess the link between maternal contact with infants and epigenetic signatures in children 4–5 years later, with respect to multiple levels of child-level factors, including genetic variation and infant distress. We first investigated DNAm at four candidate genes: the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), μ-opioid receptor M1 (OPRM1) and oxytocin receptor (OXTR; related to the neurobiology of social bonds), and brain-derived neurotrophic factor (BDNF; involved in postnatal plasticity). Although no candidate gene DNAm sites significantly associated with early postnatal contact, when we next examined DNAm across the genome, differentially methylated regions were identified between high and low contact groups. Using a different application of epigenomic information, we also quantified epigenetic age, and report that for infants who received low contact from caregivers, greater infant distress was associated with younger epigenetic age. These results suggested that early postnatal contact has lasting associations with child biology.