Parental mental health, socioeconomic position and the risk of asthma in children-a nationwide Danish register study

BACKGROUND: Parental mental illness affects child health. However, less is known about the impact of different severities of maternal depression and anxiety as well as other mental health conditions. The objective of this study was to examine the impact of different severities of maternal and paternal mental health conditions on child asthma. METHODS: This nationwide, register-based cohort study included all children in Denmark born from 2000 to 2014. Exposure was parental mental health conditions categorized in three severities: minor (treated at primary care settings), moderate (all ICD-10 F-diagnoses given at psychiatric hospital) and severe (diagnoses of severe mental illness). The children were followed from their third to sixth birthday. Child asthma was identified by prescribed medication and hospital-based diagnoses. Incidence rate ratios were calculated using negative binomial regression analyses. RESULTS: The analyses included 925 288 children; 26% of the mothers and 16% of the fathers were classified with a mental health condition. Exposed children were more likely to have asthma (10.6-12.0%) compared with unexposed children (8.5-9.0%). The three severities of mental health conditions of the mother and the father increased the risk of child asthma, most evident for maternal exposure. Additive interaction between maternal mental health conditions and disadvantaged socioeconomic position was found. CONCLUSION: We found an increased risk of asthma in exposed children, highest for maternal exposure. Not only moderate and severe, but also minor mental health conditions increased the risk of child asthma. The combination of mental health condition and disadvantaged socioeconomic position for mothers revealed a relative excess risk

Managing COVID-19 within and across health systems:why we need performance intelligence to coordinate a global response

Background The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems’ decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic. Discussion A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance. Conclusion Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution

Liver cirrhosis, other liver diseases, and risk of hospitalisation for intracerebral haemorrhage: A Danish population-based case-control study

<p>Abstract</p> <p>Background</p> <p>Liver diseases are suspected risk factors for intracerebral haemorrhage (ICH). We conducted a population-based case-control study to examine risk of ICH among hospitalised patients with liver cirrhosis and other liver diseases.</p> <p>Methods</p> <p>We used data from the hospital discharge registries (1991–2003) and the Civil Registration System in Denmark, to identify 3,522 cases of first-time hospitalisation for ICH and 35,173 sex- and age-matched population controls. Among cases and controls we identified patients with a discharge diagnosis of liver cirrhosis or other liver diseases before the date of ICH. We computed odds ratios for ICH by conditional logistic regressions, adjusting for a number of confounding factors.</p> <p>Results</p> <p>There was an increased risk of ICH for patients with alcoholic liver cirrhosis (adjusted OR = 4.8, 95% CI: 2.7–8.3), non-alcoholic liver cirrhosis (adjusted OR = 7.7, 95% CI: 2.0–28.9) and non-cirrhotic alcoholic liver disease (adjusted OR = 5.4, 95%CI:3.1–9.5) but not for patients with non-cirrhotic non-alcoholic liver diseases (adjusted OR = 0.9, 95%CI:0.5–1.6). The highest risk was found among women with liver cirrhosis (OR = 8.9, 95%CI:2.9–26.7) and for patients younger than 70 years (OR = 6.1, 95%CI:3.4–10.9). There were no sex- or age-related differences in the association between other liver diseases (alcoholic or non-alcoholic) and hospitalisation with ICH.</p> <p>Conclusion</p> <p>Patients with liver cirrhosis and non-cirrhotic alcoholic liver disease have a clearly increased risk for ICH.</p

Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population

BACKGROUND: Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients. METHODS: We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year. RESULTS: Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48). The corresponding RR was 1.34 (95% CI, 1.06–1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62) with naproxen to 1.38 (95% CI, 1.00–1.90) with diclofenac. CONCLUSION: This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs

Hierarchy measure for complex networks

Nature, technology and society are full of complexity arising from the intricate web of the interactions among the units of the related systems (e.g., proteins, computers, people). Consequently, one of the most successful recent approaches to capturing the fundamental features of the structure and dynamics of complex systems has been the investigation of the networks associated with the above units (nodes) together with their relations (edges). Most complex systems have an inherently hierarchical organization and, correspondingly, the networks behind them also exhibit hierarchical features. Indeed, several papers have been devoted to describing this essential aspect of networks, however, without resulting in a widely accepted, converging concept concerning the quantitative characterization of the level of their hierarchy. Here we develop an approach and propose a quantity (measure) which is simple enough to be widely applicable, reveals a number of universal features of the organization of real-world networks and, as we demonstrate, is capable of capturing the essential features of the structure and the degree of hierarchy in a complex network. The measure we introduce is based on a generalization of the m-reach centrality, which we first extend to directed/partially directed graphs. Then, we define the global reaching centrality (GRC), which is the difference between the maximum and the average value of the generalized reach centralities over the network. We investigate the behavior of the GRC considering both a synthetic model with an adjustable level of hierarchy and real networks. Results for real networks show that our hierarchy measure is related to the controllability of the given system. We also propose a visualization procedure for large complex networks that can be used to obtain an overall qualitative picture about the nature of their hierarchical structure.Comment: 29 pages, 9 figures, 4 table

Insulin resistance, adiponectin and adverse outcomes following elective cardiac surgery: a prospective follow-up study

<p>Abstract</p> <p>Background</p> <p>Insulin resistance and adiponectin are markers of cardio-metabolic disease and associated with adverse cardiovascular outcomes. The present study examined whether preoperative insulin resistance or adiponectin were associated with short- and long-term adverse outcomes in non-diabetic patients undergoing elective cardiac surgery.</p> <p>Methods</p> <p>In a prospective study, we assessed insulin resistance and adiponectin levels from preoperative fasting blood samples in 836 patients undergoing cardiac surgery. Population-based medical registries were used for postoperative follow-up. Outcomes included all-cause death, myocardial infarction or percutaneous coronary intervention, stroke, re-exploration, renal failure, and infections. The ability of insulin resistance and adiponectin to predict clinical adverse outcomes was examined using receiver operating characteristics.</p> <p>Results</p> <p>Neither insulin resistance nor adiponectin were statistically significantly associated with 30-day mortality, but adiponectin was associated with an increased 31-365-day mortality (adjusted odds ratio 2.9 [95% confidence interval 1.3-6.4]) comparing the upper quartile with the three lower quartiles. Insulin resistance was a poor predictor of adverse outcomes. In contrast, the predictive accuracy of adiponectin (area under curve 0.75 [95% confidence interval 0.65-0.85]) was similar to that of the EuroSCORE (area under curve 0.75 [95% confidence interval 0.67-0.83]) and a model including adiponectin and the EuroSCORE had an area under curve of 0.78 [95% confidence interval 0.68-0.88] concerning 31-365-day mortality.</p> <p>Conclusions</p> <p>Elevated adiponectin levels, but not insulin resistance, were associated with increased mortality and appear to be a strong predictor of long-term mortality. Additional studies are warranted to further clarify the possible clinical role of adiponectin assessment in cardiac surgery.</p> <p>Trial Registration</p> <p>The Danish Data Protection Agency; reference no. 2007-41-1514.</p

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

A cross-sectional study of different patterns of oral contraceptive use among premenopausal women and circulating IGF-1: implications for disease risk

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-1) is important in normal growth, development, and homeostasis. Current use of oral contraceptives (OC) decreases IGF-1 concentrations; however, the effect of past use, age/timing of use, and type of OC used on IGF-1 levels is unknown. OC are the most commonly used form of birth control worldwide. Both IGF-1 and OC use have been linked to premenopausal breast and colorectal cancers, osteoporosis and cardiovascular disease (CVD). Understanding the effects of different patterns of OC use on IGF-1 levels may offer insight into its influence on disease risk in young women.</p> <p>Methods</p> <p>In a cross-sectional study of 328 premenopausal women ages 18 to 21 and 31 to 40 we examined the relationship between different patterns of OC use and circulating IGF-1 using adjusted linear regression analysis. Information on OC use was obtained through an interviewer administered questionnaire. Plasma IGF-1 was assessed with enzyme linked immunosorbent assay (ELISA).</p> <p>Results</p> <p>Among women aged 18 to 21, ever OC use was significantly associated with decreased IGF-1 levels compared to never use (β = -57.2 ng/ml, 95% confidence interval (CI): -88.7, -25.8). Among women aged 31 to 40, past users who first used OC at 25 years of age or older (β = 43.8 ng/ml, 95% CI: 8.8, 78.8), in the last 15 years (β = 35.1 ng/ml, 95% CI: 9.3, 61.0) or after 1995 (β = 46.6 ng/ml, 95% CI: 13.4, 79.8) had significantly higher IGF-1 levels compared to never users.</p> <p>Conclusion</p> <p>This is the first study to highlight the long term effects of OC use after cessation on IGF-1 levels among premenopausal women, which previously were thought to be transitory. Future studies of past use and IGF-1 levels are required and must consider age/timing of use and type/generation of OC used. Additional studies are needed to confirm the potential mediation of IGF-1 levels in the links between OC use and health outcomes.</p

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated