Contextual Determinants of Childhood Injury: A Systematic Review of Studies With Multilevel Analytic Methods

Background. The definition of injury that underpins the contemporary approach to injury prevention is an etiological definition relating to bodily damage arising from transfer of energy to tissues of the body beyond the limits compatible with physiological function. Causal factors proximal to the energy transfer are nested within a more complex set of contextual determinants. For effective injury control, understanding of these determinants is critical.Objectives. The primary aims of this study were to describe the area-level determinants that have been included in multilevel analyses of childhood injury and to quantify the relationships between these area-level exposures and injury outcomes.Search methods. We conducted a systematic review of peer-reviewed, English-language literature published in scientific journals between January 1997 and July 2014, reporting studies that employed multilevel analyses to quantify the eco-epidemiological causation of physical unintentional injuries to children aged 16 years and younger. We conducted and reported the review in accordance with the PRISMA guidelines.Selection criteria. We included etiological studies of causal risk factors for unintentional traumatic injuries to children aged 0 to 16 years. Methodological inclusion criteria were as follows:

• Epidemiological studies quantifying the relationship between risk factors (at various levels) and injury occurrence in the individual;
• Studies that recognized individual exposure and at least 1 higher level of exposure with units at lower levels or microunits (e.g., individuals) nested within units at higher levels or macrounits (e.g., areas or neighborhoods);
• Injury outcomes (dependent variable) examined at the individual level; and
• Central analytic techniques belonging to the following categories: multilevel models, hierarchical models, random effects models, random coefficient models, covariance components models, variance components models, and mixed models.

We combined criteria from the checklist described by the Cochrane Effective Practice and Organization of Care Review Group with factors in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement, and we used several quality assessment items from other injury-related systematic reviews to create a quality assessment checklist for this review.Data collection and analysis. Two authors independently extracted data and selected analysis features for the included studies by using preformatted tables. They extracted information as reported in the articles. We determined statistical significance of estimates and effects by using the conventional threshold, P < .05. Any differences in the information extracted were resolved by discussion between authors and by specifically rereading and rechecking the facts as reported in the relevant articles. We tabulated results from the final multilevel model(s) in each of the included articles with key aspects summarized in text. Interpretations of the results and identification of key issues raised by the collated material are reported in the Discussion section of this article.Main results. We identified 11 967 articles from the electronic search with only 14 being included in the review after a detailed screening and selection process. Nine of the 14 studies identified significant fixed effects at both the area and individual levels. The area-level variables most consistently associated with child injury rates related to poverty, education, employment, and access to services. There was some evidence that injury rates were lower in areas scoring well on area-level summary measures of neighborhood safety. There was marked variation in the methods used and in the mapping of measured variables onto the conceptual model of ecological causation.Author conclusions. These results help establish the scope for the public policy approach to injury prevention. More consistent reporting of multilevel study results would aid future interpretation and translation of such findings.PLAIN-LANGUAGE SUMMARY: Injury remains the leading cause of childhood deaths in many parts of the world. Part of the variation in child injury rates between populations can be explained by the different social and physical environments within which children live. We reviewed the current state of knowledge in this area.We examined 14 qualifying research articles relevant to the area of interest. Results of the review show that features of the social and physical environments most consistently associated with child injury rates involve neighborhood safety, poverty, levels of education, and access to services. Because there have been so few research projects conducted on this topic, and because of the wide variation in the methods used, existing knowledge does not offer a strong basis for explaining how the environments in which children live influence their risk of injury.Public policy offers great potential (e.g., through allocation of public resources, activities of social institutions, design of public spaces) to facilitate solutions to the problem of injury. Although the evidence provided by this review is somewhat limited in scope, what it does provide is critically important for the development of future research and future public policy initiatives.The definition of injury that underpins the contemporary approach to injury prevention is an etiological definition relating to bodily damage arising from transfer of energy to tissues of the body beyond the limits compatible with physiological function.1,2 Causal factors proximal to the energy transfer are nested within a more complex set of contextual determinants.3 For effective injury control, understanding of these contexts is critical.4The most common characterization of the context in which energy transfer occurs has been in terms of the social determinants of health literature.5 A systematic review of all articles published between 1960 and 2002 that quantified the role of socioeconomic determinants of injury identified 10 studies with data analyzed only at the individual level, 5 that used area-level analysis, and only 1 study that employed multilevel statistics.6 Overall, authors reported a strong, inverse association between socioeconomic status and unintentional injuries, but noted varied patterns depending on injury cause, setting, population, and level of analyses.6 There was also a general consensus among authors that the mixed results across the published literature may have been because the role of context as a determinant of injury was more nuanced than could be detected by the coarse measurements and methods used, and that the field needed to develop further in terms of measurement, conceptualization of cause, and analytic sophistication if it were to adequately describe the complex causal pathways.Since 2002, several qualitative efforts have been made to apply and adapt the developing concepts of ecological public health to the specific issue of injury causation.7–10 In 2010, Pickett et al. noted that the field of injury control research was starting to benefit from a recent application of the multilevel concept of injury causation, stated a priori, to guide more innovative etiological modeling.11 However, to date there remain few accounts in the literature of quantitative studies whose primary aim has been to elucidate ecological causation by using appropriate multilevel statistics. To the authors’ knowledge, there have been no published studies that have delineated the relevant multilevel causal factors for a given injury type and then developed, implemented, and evaluated a whole-of-population injury prevention program based on this eco-epidemiological framework.Interest in the need to understand the context within which injury occurs has been heightened by developments in the public policy approach to injury prevention. Public policy has long been an important tool for injury prevention practitioners, as the logical final step in the progression from knowledge to practice (e.g., the mandated use of child car seats and bike helmets to ensure widespread uptake). More recently, injury prevention practitioners have formally explored policy frameworks and approaches, such as Kingdon’s streams approach,12 that focus on the public domain, and on how and why policy issues rise and fall from the government agenda.13 In their explanation of road safety as a social issue, Johnson et al.14 discuss the role of public constituency, committed societal leadership, safety climate, an appropriate infrastructure, cooperation and coordination among all stakeholders, and a long-term perspective as critical elements of societal intervention to eliminate serious injury and death from road transport. In epidemiological terms, these social institutions are the area-level factors in a multilevel causal model of road crash injury that when optimized by practitioner action become components of the overall preventive intervention.Activities of social institutions, allocation of public resources, and design of public spaces are specified by public policy. Policy has a more direct influence on area-level than on individual-level factors. Thus, understanding the relationship between these area-level factors, the downstream individual-level behaviors, and the risk of child injury may be helpful in maximizing the effectiveness of child injury interventions at the population level.As the basis for encouraging further the development of an ecological approach to injury prevention, we have undertaken a systematic review to identify, collate, and synthesize the current quantitative evidence from studies that have used formal multilevel statistical methods to examine the causation of childhood injury. The primary aims of this study were to describe the multilevel determinants of childhood injury represented in the included studies and to quantify the relationships between these multilevel level exposures and injury outcomes.     

Management of atrial fibrillation: two decades of progress — a scientific statement from the European Cardiac Arrhythmia Society

Journal of Interventional Cardiac Electrophysiology - Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. The aim of this review was to evaluate the...     

Could associations between breastfeeding and insulin‐like growth factors underlie associations of breastfeeding with adult chronic disease? The Avon Longitudinal Study of Parents and Children

Objective The influence of infant feeding method (breast/formula) on growth factor levels could underlie associations of breastfeeding with childhood growth and risk factors for cardiovascular disease. We investigated associations of having been breastfed with serum IGF‐I and IGFBP‐3 in childhood. Methods Prospective birth cohort study (subsample of the Avon Longitudinal Study of Parents and Children, UK) based on 871 children born in 1991/1992 who underwent clinical follow‐up and blood tests at age 7–8 years. A total of 488 (56%) children had complete data. Results In children with complete data, the age‐ and sex‐standardized IGF‐I levels of those who were partially or exclusively breastfed were 6·1 and 13·8 ng/ml higher, respectively, than those who were never breastfed (increase in IGF‐I levels per category of breastfeeding exclusivity: 7·1 ng/ml; 95% CI: 0·3–13·9; P = 0·04). In models also controlling for birthweight, gestational age, mother's age, and socioeconomic and dietary factors, the breastfeeding–IGF‐I association was attenuated (regression coefficient: 3·3 ng/ml; ?4·2–10·7; P = 0·4); further adjustment for IGFBP‐3 made little difference (regression coefficient: 4·1 ng/ml; ?2·8–10·9; P = 0·2). There was little evidence for an association between breastfeeding and IGFBP‐3 or the molar ratio IGF‐I/IGFBP‐3. Conclusions The positive association between breastfeeding and IGF‐I could be due to residual confounding or to chance. Nevertheless, the magnitude of the fully adjusted effect estimate and the novelty of the association suggest that larger studies should now be conducted to confirm or refute the hypothesis that variations in IGF‐I by infant feeding mode explain associations of breastfeeding with health in later life.     

Determinants of Intima-Media Thickness in the Young: The ALSPAC Study

ObjectivesThis study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years.BackgroundGreater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood.MethodsAssociations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences.ResultsFat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: ?0.0032; 95% CI: 0.004 to ?0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor?associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor.ConclusionsSubtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood.     

A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide

NOD2, a NOD-like receptor (NLR), is an intracellular sensor of bacterial muramyl dipeptide (MDP) that was suggested to promote secretion of the proinflammatory cytokine IL-1beta. Yet, the molecular mechanism by which NOD2 can stimulate IL-1beta secretion, and its biological significance were heretofore unknown. We found that NOD2 through its N-terminal caspase recruitment domain directly binds and activates caspase-1 to trigger IL-1beta processing and secretion in MDP-stimulated macrophages, whereas the C-terminal leucine-rich repeats of NOD2 prevent caspase-1 activation in nonstimulated cells. MDP challenge induces the association of NOD2 with another NLR protein, NALP1, and gel filtration analysis revealed the formation of a complex consisting of NOD2, NALP1, and caspase-1. Importantly, Bacillus anthracis infection induces IL-1beta secretion in a manner that depended on caspase-1 and NOD2. In vitro, Anthrax lethal toxin strongly potentiated IL-1beta secretion, and that response was NOD2 and caspase-1-dependent. Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion.     

Dose response of experimental Pseudomonas endophthalmitis to ciprofloxacin, gentamicin, and imipenem: evidence for resistance to "late" treatment of infections

Single intravitreal doses of ciprofloxacin, gentamicin, or imipenem were administered to rabbits with pseudomonas endophthalmitis for determination of the maximally effective dose. Treatment was given 24 hr ("early") or 48 hr ("late") after infection. With early treatment the dose-response relationship between the drug concentration and the diminution in bacterial counts in the vitreous humor was linear with all three drugs. By contrast, with late treatment the same vitreal concentrations had no significant effect on bacterial counts. The failure of late treatment was not due to an increased rate of clearance of drugs from the eyes and could not be reproduced with a similar bacterial inoculum in vitro. Bacteria cultured from treated eyes were fully sensitive when plated directly onto drug-containing agar. The poor bactericidal effect of late treatment may in part be related to transient phenotypic alterations in the bacteria in response to changes in the environment of infection such as hypoxia, low pH, and exhaustion of critical bacterial nutrients.